Rafi Ahmed

How Does Cross-Reactive Stimulation Affect the Longevity of CD8þ T Cell Memory? (2009)

Vitaly V. Ganusov, Sergei S. Pilyugin, Rafi Ahmed, Rustom Antia

Immunological memory—the ability to ‘‘remember’ ’ previously encountered pathogens and respond faster upon reexposure is a central feature of the immune response in vertebrates. The...

How Does Cross-Reactive Stimulation Affect the Longevity of CD8+ T Cell Memory? (2006)

Vitaly V. Ganusov, Sergei S. Pilyugin, Rafi Ahmed, Rustom Antia

Immunological memory—the ability to “remember” previously encountered pathogens and respond faster upon re-exposure is a central feature of the immune response in vertebrates. The...

How does cross-reactive stimulation affect the longevity of CD8+ T cell memory? (2006)

Vitaly V. Ganusov, Sergei Pilyugin, Rafi Ahmed, Rustom Antia

Immunological memory --- the ability to ``remember' previously encountered pathogens and respond faster upon re-exposure is a central feature of the immune response in vertebrates. The cross-reactive...

Enhanced Expression of Cell Cycle Regulatory Genes in Virus-Specific (2004)

Memory Cd, T Cells, Donald R. Latner, Susan M. Kaech, Rafi Ahmed

Unlike naive CD8 � T cells, antigen-experienced memory CD8 � T cells persist over time due to their unique ability to homeostatically proliferate. It was hypothesized that memory cells might...

Prolonged presence of effector-memory CD8 T cells in the central nervous system after dengue virus encephalitis (2003)

Murali-Krishna, Kaja, Ahmed, Rafi

Dengue virus infection in the central nervous system (CNS) of immunized mice results in a strong influx of CD8 T cells into the brain. Whereas the kinetics of the splenic antiviral response are...

Recruitment times, proliferation, and apoptosis rates during the CD8 + T-cell response to lymphocytic choriomeningitis virus (2001)

Mihaela Oprea, Rustom Antia, Kaja Murali-krishna, Rafi Ahmed, Alan S. Perelson

The specific CD8 � T-cell response during acute lymphocytic choriomeningitis virus (LCMV) infection of mice is characterized by a rapid proliferation phase, followed by a rapid death phase and...

Chimeric Yellow Fever/Dengue Virus as a Candidate Dengue Vaccine: Quantitation of the Dengue Virus-Specific CD8 T-Cell Response (2000)

Van Der Most, Robbert G., Murali-Krishna, Kaja, Ahmed, Rafi, Strauss, James H.

We have constructed a chimeric yellow fever/dengue (YF/DEN) virus, which expresses the premembrane (prM) and envelope (E) genes from DEN type 2 (DEN-2) virus in a YF virus (YFV-17D) genetic...

Automatic Importation of Relational Schemas in Pegasus (1993)

Joseph Albert Rafi, Joseph Albert, Rafi Ahmed, Mohammed Ketabchi, William Kent, Ming-chien Shan

This paper describes a technique for importing automatically an external relational schema into Pegasus, a heterogeneous, multidatabase system. The Pegasus data model is a functional object model...

Object identification in multidatabase systems (1993)

William Kent, Rafi Ahmed, Joseph Albert, Mohammad Ketabchi, Ming-chien Shan

In the Pegasus prototype multidatabase system, the key to the problem of object identity is a differentiation between the view of a data administrator, capturing all the underlying discrepancies and...

Molecular basis of organ-specific selection of viral variants during chronic infection (1991)

Ahmed, Rafi, Hahn, Chang S., Somasundaram, T., Villarete, Lorelie, Matloubian, Mehrdad, Strauss, James H.

Viral variants of different phenotypes are present in the central nervous system (CNS) and lymphoid tissues of carrier mice infected at birth with the Armstrong strain of lymphocytic choriomeningitis...

The lactose system in Thermus sp. T2. (1974)

Ahmed, Rafi.

Thesis (M.S.)--Idaho State University, 1974.

Models of immune memory: On the role of cross-reactive stimulation, competition, and homeostasis in maintaining immune memory

Antia, Rustom, Pilyugin, Sergei S., Ahmed, Rafi

There has been much debate on the contribution of processes such as the persistence of antigens, cross-reactive stimulation, homeostasis, competition between different lineages of lymphocytes, and...

Altered lymphocyte responses and cytokine production in mice deficient in the X-linked lymphoproliferative disease gene SH2D1A/DSHP/SAP

Czar, Michael J., Kersh, Ellen N., Mijares, Lilia A., Lanier, Gibson, Lewis, Jennifer, Yap, George, ...

We have introduced a targeted mutation in SH2D1A/DSHP/SAP, the gene responsible for the human genetic disorder X-linked lymphoproliferative disease (XLP). SLAM-associated protein (SAP)-deficient mice...

A Role for Perforin in Downregulating T-Cell Responses during Chronic Viral Infection

Matloubian, Mehrdad, Suresh, M., Glass, Alison, Galvan, Marisa, Chow, Kit, Whitmire, Jason K., ...

Cytotoxic T cells secrete perforin to kill virus-infected cells. In this study we show that perforin also plays a role in immune regulation. Perforin-deficient (perf −/−) mice chronically...

Long-Term CD4 Th1 and Th2 Memory following Acute Lymphocytic Choriomeningitis Virus Infection

Whitmire, Jason K., Asano, Mary S., Murali-Krishna, Kaja, Suresh, M., Ahmed, Rafi

CD4 T cells play a central role in viral immunity. They provide help for B cells and CD8 T cells and can act as effectors themselves. Despite their importance, relatively little is known about the...

Chimeric Yellow Fever/Dengue Virus as a Candidate Dengue Vaccine: Quantitation of the Dengue Virus-Specific CD8 T-Cell Response

Van Der Most, Robbert G., Murali-Krishna, Kaja, Ahmed, Rafi, Strauss, James H.

We have constructed a chimeric yellow fever/dengue (YF/DEN) virus, which expresses the premembrane (prM) and envelope (E) genes from DEN type 2 (DEN-2) virus in a YF virus (YFV-17D) genetic...

Passive Transfer of Antibodies Protects Immunocompetent and Immunodeficient Mice against Lethal Ebola Virus Infection without Complete Inhibition of Viral Replication

Gupta, Manisha, Mahanty, Siddhartha, Bray, Mike, Ahmed, Rafi, Rollin, Pierre E.

Ebola hemorrhagic fever is a severe, usually fatal illness caused by Ebola virus, a member of the filovirus family. The use of nonhomologous immune serum in animal studies and blood from survivors in...

Recruitment Times, Proliferation, and Apoptosis Rates during the CD8+ T-Cell Response to Lymphocytic Choriomeningitis Virus

De Boer, Rob J., Oprea, Mihaela, Antia, Rustom, Murali-Krishna, Kaja, Ahmed, Rafi, Perelson, Alan S.

The specific CD8+ T-cell response during acute lymphocytic choriomeningitis virus (LCMV) infection of mice is characterized by a rapid proliferation phase, followed by a rapid death phase and...

In Vivo Selection of a Lymphocytic Choriomeningitis Virus Variant That Affects Recognition of the GP33-43 Epitope by H-2Db but Not H-2Kb

Puglielli, Maryann T., Zajac, Allan J., Van Der Most, Robbert G., Dzuris, John L., Sette, Alessandro, Altman, John D., ...

CD8 T cells drive the protective immune response to lymphocytic choriomeningitis virus (LCMV) infection and are thus a determining force in the selection of viral variants. To examine how escape...

Cytotoxic T-Lymphocyte Epitopes Fused to Anthrax Toxin Induce Protective Antiviral Immunity

Doling, Amy M., Ballard, Jimmy D., Shen, Hao, Krishna, Kaja Murali, Ahmed, Rafi, Collier, R. John, ...

We have investigated the use of the protective antigen (PA) and lethal factor (LF) components of anthrax toxin as a system for in vivo delivery of cytotoxic T-lymphocyte (CTL) epitopes. During...

Recombinant Vaccinia Virus-Induced T-Cell Immunity: Quantitation of the Response to the Virus Vector and the Foreign Epitope

Harrington, Laurie E., Most, Robbert Van Der, Whitton, J. Lindsay, Ahmed, Rafi

Recombinant vaccinia viruses (rVV) have been extensively used as vaccines, but there is little information about the total magnitude of the VV-specific T-cell response and how this compares to the...

Role of Lymphotoxin α in T-Cell Responses during an Acute Viral Infection

Suresh, M., Lanier, Gibson, Large, Mary Katherine, Whitmire, Jason K., Altman, John D., Ruddle, Nancy H., ...

The importance of lymphotoxin α (LTα) in lymphoid organogenesis is well established. Although LTα has been implicated in the pathogenesis of T-cell-mediated immunopathologies, the requirement for...

Evidence for Antibody-Mediated Enhancement of Simian Immunodeficiency Virus (SIV) Gag Antigen Processing and Cross Presentation in SIV-Infected Rhesus Macaques

Villinger, Francois, Mayne, Ann E., Bostik, Pavel, Mori, Kazuyasu, Jensen, Peter E., Ahmed, Rafi, ...

By using the dominant simian immunodeficiency virus (SIV) Gag Mamu-A01 restricted major histocompatibility complex (MHC) class I epitope p11CM, we demonstrate antibody-mediated enhanced MHC class I...

Viral Persistence Alters CD8 T-Cell Immunodominance and Tissue Distribution and Results in Distinct Stages of Functional Impairment

Wherry, E. John, Blattman, Joseph N., Murali-Krishna, Kaja, Van Der Most, Robbert, Ahmed, Rafi

Chronic viral infections often result in ineffective CD8 T-cell responses due to functional exhaustion or physical deletion of virus-specific T cells. However, how persisting virus impacts various...

Heterologous immunity provides a potent barrier to transplantation tolerance

Adams, Andrew B., Williams, Matthew A., Jones, Thomas R., Shirasugi, Nozomu, Durham, Megan M., Kaech, Susan M., ...

Many strategies have been proposed to induce tolerance to transplanted tissue in rodents; however, few if any have shown equal efficacy when tested in nonhuman primate transplant models. We...

Genetic Variation During Persistent Reovirus Infection: Presence of Extragenically Suppressed Temperature-Sensitive Lesions in Wild-Type Virus Isolated from Persistently Infected L Cells

Ahmed, Rafi, Chakraborty, P. R., Graham, A. F., Ramig, R. F., Fields, B. N.

Persistent reovirus infection of L cells was established with a serially passaged stock of temperature-sensitive (ts) mutant C(447) containing greater than 90% defective interfering particles. Within...

Persistent Infection with Ebola Virus under Conditions of Partial Immunity

Gupta, Manisha, Mahanty, Siddhartha, Greer, Patricia, Towner, Jonathan S., Shieh, Wun-Ju, Zaki, Sherif R., ...

Ebola hemorrhagic fever in humans is associated with high mortality; however, some infected hosts clear the virus and recover. The mechanisms by which this occurs and the correlates of protective...

Complexity of CNC Transcription Factors As Revealed by Gene Targeting of the Nrf3 Locus

Derjuga, Anna, Gourley, Tania S., Holm, Teresa M., Heng, Henry H. Q., Shivdasani, Ramesh A., Ahmed, Rafi, ...

Cap'n'collar (CNC) family basic leucine zipper transcription factors play crucial roles in the regulation of mammalian gene expression and development. To determine the in vivo function of the CNC...

Enhanced Expression of Cell Cycle Regulatory Genes in Virus-Specific Memory CD8+ T Cells

Latner, Donald R., Kaech, Susan M., Ahmed, Rafi

Unlike naive CD8+ T cells, antigen-experienced memory CD8+ T cells persist over time due to their unique ability to homeostatically proliferate. It was hypothesized that memory cells might...

Antigen-independent memory CD8 T cells do not develop during chronic viral infection

Wherry, E. John, Barber, Daniel L., Kaech, Susan M., Blattman, Joseph N., Ahmed, Rafi

Memory T cells can persist for extended periods in the absence of antigen, and long-term T cell immunity is often seen after acute infections. Paradoxically, there have been observations suggesting...

The CD4 molecule on CD8+ T lymphocytes directly enhances the immune response to viral and cellular antigens

Kitchen, Scott G., Whitmire, Jason K., Jones, Nicole R., Galic, Zoran, Kitchen, Christina M. R., Ahmed, Rafi, ...

CD8+ T lymphocytes play a major role in cellular-mediated immune responses to foreign antigen. We have previously demonstrated that costimulation of purified human CD8+ T cells induces de novo...

BCL6b mediates the enhanced magnitude of the secondary response of memory CD8+ T lymphocytes

Manders, Peter M., Hunter, Patricia J., Telaranta, Aino I., Carr, James M., Marshall, Jennifer L., Carrasco, Marlene, ...

A characteristic of the secondary response of CD8+ T cells that distinguishes it from the primary response is the generation of greater numbers of effector cells. Because effector CD8+ T cells are...

Chimeric Influenza Virus Hemagglutinin Proteins Containing Large Domains of the Bacillus anthracis Protective Antigen: Protein Characterization, Incorporation into Infectious Influenza Viruses, and Antigenicity

Li, Zhu-Nan, Mueller, Scott N., Ye, Ling, Bu, Zhigao, Yang, Chinglai, Ahmed, Rafi, ...

Large polypeptides of the Bacillus anthracis protective antigen (PA) were inserted into an influenza A virus hemagglutinin glycoprotein (HA), and the chimeric proteins were functionally characterized...

Low CD8 T-Cell Proliferative Potential and High Viral Load Limit the Effectiveness of Therapeutic Vaccination

Wherry, E. John, Blattman, Joseph N., Ahmed, Rafi

Therapeutic vaccination has the potential to boost immune responses and enhance viral control during chronic infections. However, many therapeutic vaccination approaches have fallen short of...

How Does Cross-Reactive Stimulation Affect the Longevity of CD8+ T Cell Memory?

Ganusov, Vitaly V, Pilyugin, Sergei S, Ahmed, Rafi, Antia, Rustom

Immunological memory—the ability to “remember” previously encountered pathogens and respond faster upon re-exposure is a central feature of the immune response in vertebrates. The...

Models of immune memory: On the role of cross-reactive stimulation, competition, and homeostasis in maintaining immune memory

Antia, Rustom, Pilyugin, Sergei S., Ahmed, Rafi

There has been much debate on the contribution of processes such as the persistence of antigens, cross-reactive stimulation, homeostasis, competition between different lineages of lymphocytes, and...

Altered lymphocyte responses and cytokine production in mice deficient in the X-linked lymphoproliferative disease gene SH2D1A/DSHP/SAP

Czar, Michael J., Kersh, Ellen N., Mijares, Lilia A., Lanier, Gibson, Lewis, Jennifer, Yap, George, ...

We have introduced a targeted mutation in SH2D1A/DSHP/SAP, the gene responsible for the human genetic disorder X-linked lymphoproliferative disease (XLP). SLAM-associated protein (SAP)-deficient mice...

A Role for Perforin in Downregulating T-Cell Responses during Chronic Viral Infection

Matloubian, Mehrdad, Suresh, M., Glass, Alison, Galvan, Marisa, Chow, Kit, Whitmire, Jason K., ...

Cytotoxic T cells secrete perforin to kill virus-infected cells. In this study we show that perforin also plays a role in immune regulation. Perforin-deficient (perf −/−) mice chronically...

Long-Term CD4 Th1 and Th2 Memory following Acute Lymphocytic Choriomeningitis Virus Infection

Whitmire, Jason K., Asano, Mary S., Murali-Krishna, Kaja, Suresh, M., Ahmed, Rafi

CD4 T cells play a central role in viral immunity. They provide help for B cells and CD8 T cells and can act as effectors themselves. Despite their importance, relatively little is known about the...

Chimeric Yellow Fever/Dengue Virus as a Candidate Dengue Vaccine: Quantitation of the Dengue Virus-Specific CD8 T-Cell Response

Van Der Most, Robbert G., Murali-Krishna, Kaja, Ahmed, Rafi, Strauss, James H.

We have constructed a chimeric yellow fever/dengue (YF/DEN) virus, which expresses the premembrane (prM) and envelope (E) genes from DEN type 2 (DEN-2) virus in a YF virus (YFV-17D) genetic...

Passive Transfer of Antibodies Protects Immunocompetent and Immunodeficient Mice against Lethal Ebola Virus Infection without Complete Inhibition of Viral Replication

Gupta, Manisha, Mahanty, Siddhartha, Bray, Mike, Ahmed, Rafi, Rollin, Pierre E.

Ebola hemorrhagic fever is a severe, usually fatal illness caused by Ebola virus, a member of the filovirus family. The use of nonhomologous immune serum in animal studies and blood from survivors in...

Recruitment Times, Proliferation, and Apoptosis Rates during the CD8+ T-Cell Response to Lymphocytic Choriomeningitis Virus

De Boer, Rob J., Oprea, Mihaela, Antia, Rustom, Murali-Krishna, Kaja, Ahmed, Rafi, Perelson, Alan S.

The specific CD8+ T-cell response during acute lymphocytic choriomeningitis virus (LCMV) infection of mice is characterized by a rapid proliferation phase, followed by a rapid death phase and...

In Vivo Selection of a Lymphocytic Choriomeningitis Virus Variant That Affects Recognition of the GP33-43 Epitope by H-2Db but Not H-2Kb

Puglielli, Maryann T., Zajac, Allan J., Van Der Most, Robbert G., Dzuris, John L., Sette, Alessandro, Altman, John D., ...

CD8 T cells drive the protective immune response to lymphocytic choriomeningitis virus (LCMV) infection and are thus a determining force in the selection of viral variants. To examine how escape...

Cytotoxic T-Lymphocyte Epitopes Fused to Anthrax Toxin Induce Protective Antiviral Immunity

Doling, Amy M., Ballard, Jimmy D., Shen, Hao, Krishna, Kaja Murali, Ahmed, Rafi, Collier, R. John, ...

We have investigated the use of the protective antigen (PA) and lethal factor (LF) components of anthrax toxin as a system for in vivo delivery of cytotoxic T-lymphocyte (CTL) epitopes. During...

Recombinant Vaccinia Virus-Induced T-Cell Immunity: Quantitation of the Response to the Virus Vector and the Foreign Epitope

Harrington, Laurie E., Most, Robbert Van Der, Whitton, J. Lindsay, Ahmed, Rafi

Recombinant vaccinia viruses (rVV) have been extensively used as vaccines, but there is little information about the total magnitude of the VV-specific T-cell response and how this compares to the...

Role of Lymphotoxin α in T-Cell Responses during an Acute Viral Infection

Suresh, M., Lanier, Gibson, Large, Mary Katherine, Whitmire, Jason K., Altman, John D., Ruddle, Nancy H., ...

The importance of lymphotoxin α (LTα) in lymphoid organogenesis is well established. Although LTα has been implicated in the pathogenesis of T-cell-mediated immunopathologies, the requirement for...

Evidence for Antibody-Mediated Enhancement of Simian Immunodeficiency Virus (SIV) Gag Antigen Processing and Cross Presentation in SIV-Infected Rhesus Macaques

Villinger, Francois, Mayne, Ann E., Bostik, Pavel, Mori, Kazuyasu, Jensen, Peter E., Ahmed, Rafi, ...

By using the dominant simian immunodeficiency virus (SIV) Gag Mamu-A01 restricted major histocompatibility complex (MHC) class I epitope p11CM, we demonstrate antibody-mediated enhanced MHC class I...

Viral Persistence Alters CD8 T-Cell Immunodominance and Tissue Distribution and Results in Distinct Stages of Functional Impairment

Wherry, E. John, Blattman, Joseph N., Murali-Krishna, Kaja, Van Der Most, Robbert, Ahmed, Rafi

Chronic viral infections often result in ineffective CD8 T-cell responses due to functional exhaustion or physical deletion of virus-specific T cells. However, how persisting virus impacts various...

Heterologous immunity provides a potent barrier to transplantation tolerance

Adams, Andrew B., Williams, Matthew A., Jones, Thomas R., Shirasugi, Nozomu, Durham, Megan M., Kaech, Susan M., ...

Many strategies have been proposed to induce tolerance to transplanted tissue in rodents; however, few if any have shown equal efficacy when tested in nonhuman primate transplant models. We...

Genetic Variation During Persistent Reovirus Infection: Presence of Extragenically Suppressed Temperature-Sensitive Lesions in Wild-Type Virus Isolated from Persistently Infected L Cells

Ahmed, Rafi, Chakraborty, P. R., Graham, A. F., Ramig, R. F., Fields, B. N.

Persistent reovirus infection of L cells was established with a serially passaged stock of temperature-sensitive (ts) mutant C(447) containing greater than 90% defective interfering particles. Within...

Persistent Infection with Ebola Virus under Conditions of Partial Immunity

Gupta, Manisha, Mahanty, Siddhartha, Greer, Patricia, Towner, Jonathan S., Shieh, Wun-Ju, Zaki, Sherif R., ...

Ebola hemorrhagic fever in humans is associated with high mortality; however, some infected hosts clear the virus and recover. The mechanisms by which this occurs and the correlates of protective...

Complexity of CNC Transcription Factors As Revealed by Gene Targeting of the Nrf3 Locus

Derjuga, Anna, Gourley, Tania S., Holm, Teresa M., Heng, Henry H. Q., Shivdasani, Ramesh A., Ahmed, Rafi, ...

Cap'n'collar (CNC) family basic leucine zipper transcription factors play crucial roles in the regulation of mammalian gene expression and development. To determine the in vivo function of the CNC...

Enhanced Expression of Cell Cycle Regulatory Genes in Virus-Specific Memory CD8+ T Cells

Latner, Donald R., Kaech, Susan M., Ahmed, Rafi

Unlike naive CD8+ T cells, antigen-experienced memory CD8+ T cells persist over time due to their unique ability to homeostatically proliferate. It was hypothesized that memory cells might...

Antigen-independent memory CD8 T cells do not develop during chronic viral infection

Wherry, E. John, Barber, Daniel L., Kaech, Susan M., Blattman, Joseph N., Ahmed, Rafi

Memory T cells can persist for extended periods in the absence of antigen, and long-term T cell immunity is often seen after acute infections. Paradoxically, there have been observations suggesting...

The CD4 molecule on CD8+ T lymphocytes directly enhances the immune response to viral and cellular antigens

Kitchen, Scott G., Whitmire, Jason K., Jones, Nicole R., Galic, Zoran, Kitchen, Christina M. R., Ahmed, Rafi, ...

CD8+ T lymphocytes play a major role in cellular-mediated immune responses to foreign antigen. We have previously demonstrated that costimulation of purified human CD8+ T cells induces de novo...

BCL6b mediates the enhanced magnitude of the secondary response of memory CD8+ T lymphocytes

Manders, Peter M., Hunter, Patricia J., Telaranta, Aino I., Carr, James M., Marshall, Jennifer L., Carrasco, Marlene, ...

A characteristic of the secondary response of CD8+ T cells that distinguishes it from the primary response is the generation of greater numbers of effector cells. Because effector CD8+ T cells are...

Low CD8 T-Cell Proliferative Potential and High Viral Load Limit the Effectiveness of Therapeutic Vaccination

Wherry, E. John, Blattman, Joseph N., Ahmed, Rafi

Therapeutic vaccination has the potential to boost immune responses and enhance viral control during chronic infections. However, many therapeutic vaccination approaches have fallen short of...

Chimeric Influenza Virus Hemagglutinin Proteins Containing Large Domains of the Bacillus anthracis Protective Antigen: Protein Characterization, Incorporation into Infectious Influenza Viruses, and Antigenicity

Li, Zhu-Nan, Mueller, Scott N., Ye, Ling, Bu, Zhigao, Yang, Chinglai, Ahmed, Rafi, ...

Large polypeptides of the Bacillus anthracis protective antigen (PA) were inserted into an influenza A virus hemagglutinin glycoprotein (HA), and the chimeric proteins were functionally characterized...

How Does Cross-Reactive Stimulation Affect the Longevity of CD8+ T Cell Memory?

Ganusov, Vitaly V, Pilyugin, Sergei S, Ahmed, Rafi, Antia, Rustom

Immunological memory—the ability to “remember” previously encountered pathogens and respond faster upon re-exposure is a central feature of the immune response in vertebrates. The...

Quantitating the Magnitude of the Lymphocytic Choriomeningitis Virus-Specific CD8 T-Cell Response: It Is Even Bigger than We Thought▿

Masopust, David, Murali-Krishna, Kaja, Ahmed, Rafi

Measuring the magnitudes and specificities of antiviral CD8 T-cell responses is critical for understanding the dynamics and regulation of adaptive immunity. Despite many excellent studies, the...

Liver-Infiltrating Lymphocytes in Chronic Human Hepatitis C Virus Infection Display an Exhausted Phenotype with High Levels of PD-1 and Low Levels of CD127 Expression▿

Radziewicz, Henry, Ibegbu, Chris C., Fernandez, Marina L., Workowski, Kimberly A., Obideen, Kamil, Wehbi, Mohammad, ...

The majority of people infected with hepatitis C virus (HCV) fail to generate or maintain a T-cell response effective for viral clearance. Evidence from murine chronic viral infections shows that...

Estimation of the rate of killing by cytotoxic T lymphocytes in vivo

Regoes, Roland R., Barber, Daniel L., Ahmed, Rafi, Antia, Rustom

Cytotoxic T lymphocytes (CTL) help control virus infections by killing virus-infected (target) cells. How fast do CTL find and kill target cells in vivo? Experiments allow us to follow populations of...

Antigen-Specific CD4+ T Cells Recognize Epitopes of Protective Antigen following Vaccination with an Anthrax Vaccine▿

Laughlin, Elsa M., Miller, Joseph D., James, Eddie, Fillos, Dimitri, Ibegbu, Chris C., Mittler, Robert S., ...

Detection of antigen-specific CD4+ T cells is facilitated by the use of fluorescently labeled soluble peptide-major histocompatibility complex (MHC) multimers which mirror the antigen specificity of...

Elevated Expression Levels of Inhibitory Receptor Programmed Death 1 on Simian Immunodeficiency Virus-Specific CD8 T Cells during Chronic Infection but Not after Vaccination▿

Velu, Vijayakumar, Kannanganat, Sunil, Ibegbu, Chris, Chennareddi, Lakshmi, Villinger, Francois, Freeman, Gordon J., ...

Here, we study the temporal expression of the inhibitory receptor programmed death 1 (PD-1) on simian immunodeficiency virus (SIV) Gag-specific T cells following pathogenic SIV infection or following...

Immune suppression or enhancement by CD137 T cell costimulation during acute viral infection is time dependent

Zhang, Benyue, Maris, Charles H., Foell, Juergen, Whitmire, Jason, Niu, Liguo, Song, Jing, ...

CD137 is expressed on activated T cells and ligands to this costimulatory molecule have clinical potential for amplifying CD8 T cell immunity to tumors and viruses, while suppressing CD4 autoimmune T...

Revisiting Estimates of CTL Killing Rates In Vivo

Yates, Andrew, Graw, Frederik, Barber, Daniel L., Ahmed, Rafi, Regoes, Roland R., Antia, Rustom

Recent experimental advances have allowed the estimation of the in vivo rates of killing of infected target cells by cytotoxic T lymphocytes (CTL). We present several refinements to a method applied...

Reinvigorating exhausted HIV-specific T cells via PD-1–PD-1 ligand blockade

Freeman, Gordon J., Wherry, E. John, Ahmed, Rafi, Sharpe, Arlene H.

The programmed death (PD)-1–PD-1 ligand (PD-L) pathway, which is part of the B7–CD28 family, consists of the PD-1 receptor and its two ligands PD-L1 and PD-L2. Engagement of PD-1 by its ligands...

Continuous recruitment of naive T cells contributes to heterogeneity of antiviral CD8 T cells during persistent infection

Vezys, Vaiva, Masopust, David, Kemball, Christopher C., Barber, Daniel L., O'Mara, Leigh A., Larsen, Christian P., ...

Numerous microbes establish persistent infections, accompanied by antigen-specific CD8 T cell activation. Pathogen-specific T cells in chronically infected hosts are often phenotypically and...

Yellow fever vaccine YF-17D activates multiple dendritic cell subsets via TLR2, 7, 8, and 9 to stimulate polyvalent immunity

Querec, Troy, Bennouna, Soumaya, Alkan, Sefik, Laouar, Yasmina, Gorden, Keith, Flavell, Richard, ...

The live attenuated yellow fever vaccine 17D (YF-17D) is one of the most effective vaccines available, with a 65-yr history of use in >400 million people globally. Despite this efficacy, there is...

Monkeypox-Induced Immunity and Failure of Childhood Smallpox Vaccination To Provide Complete Protection▿

Karem, Kevin L., Reynolds, Mary, Hughes, Christine, Braden, Zach, Nigam, Pragati, Crotty, Shane, ...

Following the U.S. monkeypox outbreak of 2003, blood specimens and clinical and epidemiologic data were collected from cases, defined by standard definition, and household contacts of cases to...

Viral targeting of fibroblastic reticular cells contributes to immunosuppression and persistence during chronic infection

Mueller, Scott N., Matloubian, Mehrdad, Clemens, Daniel M., Sharpe, Arlene H., Freeman, Gordon J., Gangappa, Shivaprakash, ...

Many chronic viral infections are marked by pathogen persistence and a generalized immunosuppression. The exact mechanisms by which this occurs are still unknown. Using a mouse model of persistent...

Two Roads Diverged: Interferon α/β– and Interleukin 12–mediated Pathways in Promoting T Cell Interferon γ Responses during Viral Infection

Cousens, Leslie P., Peterson, Ron, Hsu, Sang, Dorner, Andrew, Altman, John D., Ahmed, Rafi, ...

Viral infections induce CD8 T cell expansion and interferon (IFN)-γ production for defense, but the innate cytokines shaping these responses have not been identified. Although interleukin (IL)-12...

Differentiating between Memory and Effector Cd8 T Cells by Altered Expression of Cell Surface O-Glycans

Harrington, Laurie E., Galvan, Marisa, Baum, Linda G., Altman, John D., Ahmed, Rafi

Currently there are few reliable cell surface markers that can clearly discriminate effector from memory T cells. To determine if there are changes in O-glycosylation between these two cell types, we...

Interleukin 15 Is Required for Proliferative Renewal of Virus-specific Memory CD8 T Cells

Becker, Todd C., Wherry, E. John, Boone, David, Murali-Krishna, Kaja, Antia, Rustom, Ma, Averil, ...

The generation and efficient maintenance of antigen-specific memory T cells is essential for long-lasting immunological protection. In this study, we examined the role of interleukin (IL)-15 in the...

Viral Immune Evasion Due to Persistence of Activated T Cells Without Effector Function

Zajac, Allan J., Blattman, Joseph N., Murali-Krishna, Kaja, Sourdive, David J.D., Suresh, M., Altman, John D., ...

We examined the regulation of virus-specific CD8 T cell responses during chronic lymphocytic choriomeningitis virus (LCMV) infection of mice. Our study shows that within the same persistently...

Estimating the Precursor Frequency of Naive Antigen-specific CD8 T Cells

Blattman, Joseph N., Antia, Rustom, Sourdive, David J.D., Wang, Xiaochi, Kaech, Susan M., Murali-Krishna, Kaja, ...

The constraint of fitting a diverse repertoire of antigen specificities in a limited total population of lymphocytes results in the frequency of naive cells specific for any given antigen (defined as...

Conserved T Cell Receptor Repertoire in Primary and Memory CD8 T Cell Responses to an Acute Viral Infection

Sourdive, David J.D., Murali-Krishna, Kaja, Altman, John D., Zajac, Allan J., Whitmire, Jason K., Pannetier, Christophe, ...

Viral infections often induce potent CD8 T cell responses that play a key role in antiviral immunity. After viral clearance, the vast majority of the expanded CD8 T cells undergo apoptosis, leaving...

Enhancing therapeutic vaccination by blocking PD-1–mediated inhibitory signals during chronic infection

Ha, Sang-Jun, Mueller, Scott N., Wherry, E. John, Barber, Daniel L., Aubert, Rachael D., Sharpe, Arlene H., ...

Therapeutic vaccination is a potentially promising strategy to enhance T cell immunity and viral control in chronically infected individuals. However, therapeutic vaccination approaches have fallen...

Functional and genomic profiling of effector CD8 T cell subsets with distinct memory fates

Sarkar, Surojit, Kalia, Vandana, Haining, W. Nicholas, Konieczny, Bogumila T., Subramaniam, Shruti, Ahmed, Rafi

An important question in memory development is understanding the differences between effector CD8 T cells that die versus effector cells that survive and give rise to memory cells. In this study, we...

Frequency and Phenotype of Human Immunodeficiency Virus Envelope-Specific B Cells from Patients with Broadly Cross-Neutralizing Antibodies ▿

Doria-Rose, Nicole A., Klein, Rachel M., Manion, Maura M., O'Dell, Sijy, Phogat, Adhuna, Chakrabarti, Bimal, ...

Induction of broadly cross-reactive neutralizing antibodies (NAb) is an important goal for a prophylactic human immunodeficiency virus type 1 (HIV-1) vaccine. Some HIV-infected patients make a NAb...

Impact of Epitope Escape on PD-1 Expression and CD8 T-Cell Exhaustion during Chronic Infection▿

Blattman, Joseph N., Wherry, E. John, Ha, Sang-Jun, Van Der Most, Robbert G., Ahmed, Rafi

During some persistent viral infections, virus-specific T-cell responses wane due to the antigen-specific deletion or functional inactivation (i.e., exhaustion) of responding CD8 T cells. T-cell...