Bishop, Kenneth D., Harris, John E., Mordes, John P., Greiner, Dale L., Rossini, Aldo A., Czech, Michael P., ...
Recent studies have implicated the cell surface receptor Programmed Death-1 (PD-1) in numerous models of T cell anergy, though the specific mechanisms by which the PD-1 signal maintains tolerance is...
Pino, Steven C., O'Sullivan-Murphy, Bryan, Lidstone, Erich A., Thornley, Thomas B., Jurczyk, Agata, Urano, Fumihiko, ...
T cell receptor (TCR) ligation (signal one) in the presence of co-stimulation (signal two) results in downstream signals that increase protein production enabling naive T cells to fully activate and...
Thornley, Thomas B., Phillips, Nancy E., Beaudette-Zlatanova, Britte C., Markees, Thomas G., Bahl, Kapil, Brehm, Michael A., ...
TLR activation of innate immunity prevents the induction of transplantation tolerance and shortens skin allograft survival in mice treated with costimulation blockade. The mechanism by which TLR...
Different mechanisms control peripheral and central tolerance in hematopoietic chimeric mice (2007)
Yamazaki, Masahiro, Pearson, Todd, Brehm, Michael A., Miller, David M., Mangada, Julie A., Markees, Thomas G., ...
Regulatory T cells (Treg) are important in peripheral tolerance, but their role in establishing and maintaining hematopoietic mixed chimerism and generating central tolerance is unclear. We now show...
Development of new-generation HU-PBMC-NOD/SCID mice to study human islet alloreactivity (2007)
King, Marie A., Pearson, Todd, Shultz, Leonard D., Leif, Jean H., Bottino, Rita, Trucco, Massimo, ...
The use of "humanized" mice represents an appealing translational model for studies of the pathogenesis of immune-mediated diseases and for the evaluation of potential therapeutics. The utility of...
Development of new-generation HU-PBMC-NOD/SCID mice to study human islet alloreactivity (2007)
King, Marie A., Pearson, Todd, Shultz, Leonard D., Leif, Jean, Bottino, Rita, Trucco, Massimo, ...
The use of "humanized" mice represents an appealing translational model for studies of the pathogenesis of immune-mediated diseases and for the evaluation of potential therapeutics. The utility of...
Zipris, Danny, Lien, Egil, Nair, Anjali, Xie, Jenny X., Greiner, Dale L., Mordes, John P., ...
Viral infections are associated epidemiologically with the expression of type 1 diabetes in humans, but the mechanisms underlying this putative association are unknown. To investigate the role of...
Hillebrands, Jan-Luuk, Whalen, Barbara J., Visser, Jeroen T. J., Koning, Jasper, Bishop, Kenneth D., Leif, Jean, ...
Biobreeding (BB) rats model type 1 autoimmune diabetes (T1D). BB diabetes-prone (BBDP) rats develop T1D spontaneously. BB diabetes-resistant (BBDR) rats develop T1D after immunological perturbations...
ART2, a T cell surface mono-ADP-ribosyltransferase, generates extracellular poly(ADP-ribose) (2006)
Morrison, Alan R., Moss, Joel, Stevens, Linda A., Evans, James E., Farrell, Caitlin, Merithew, Eric Lee, ...
NAD functions in multiple aspects of cellular metabolism and signaling through enzymes that covalently transfer ADP-ribose from NAD to acceptor proteins, thereby altering their function. NAD is a...
TLR agonists abrogate costimulation blockade-induced prolongation of skin allografts (2006)
Thornley, Thomas B., Brehm, Michael A., Markees, Thomas G., Shultz, Leonard D., Mordes, John P., Welsh, Raymond M., ...
Costimulation blockade protocols are effective in prolonging allograft survival in animal models and are entering clinical trials, but how environmental perturbants affect graft survival remains...
Autoimmune diabetes and resistance to xenograft transplantation tolerance in NOD mice (2004)
Gordon, Ethel J., Wicker, Linda S., Peterson, Laurence B., Serreze, David V., Markees, Thomas G., Shultz, Leonard D., ...
Costimulation blockade induces prolonged rat islet and skin xenograft survival in C57BL/6 mice. Nonobese diabetic (NOD) mice, which are used to model human autoimmune diabetes, are resistant to...
TLR activation synergizes with Kilham rat virus infection to induce diabetes in BBDR rats (2004)
Zipris, Danny, Lien, Egil, Xie, Jenny X., Greiner, Dale L., Mordes, John P., Rossini, Aldo A.
Virus infection is hypothesized to be an important environmental "trigger" of type 1 diabetes in humans. We used the BBDR rat model to investigate the relationship between viral infection and...
Markees, Thomas G., Pearson, Todd, Cuthbert, Amy, Pearson, Andrea L., Shultz, Leonard D., Leif, Jean H., ...
BACKGROUND: Treatment with anti-CD154 monoclonal antibody (mAb) plus a donor-specific transfusion (DST) of spleen cells prolongs skin allograft survival in mice through a mechanism involving deletion...
Harris, John E., Bishop, Kenneth D., Phillips, Nancy E., Mordes, John P., Greiner, Dale L., Rossini, Aldo A., ...
Ag-specific immune tolerance results from the induction of cellular mechanisms that limit T cell responses to selective Ags. One of these mechanisms is characterized by attenuated proliferation and...
Pearson, Todd, Weiser, Peter, Markees, Thomas G., Serreze, David V., Wicker, Linda S., Peterson, Laurence B., ...
NOD mice develop type 1 autoimmune diabetes and exhibit genetically dominant resistance to transplantation tolerance induction. These two phenotypes are genetically separable. Costimulation blockade...
Deficiencies in gut NK cell number and function precede diabetes onset in BB rats (2004)
Todd, Derrick James, Forsberg, Eric M., Greiner, Dale L., Mordes, John P., Rossini, Aldo A., Bortell, Rita
Defects in the intestinal immune system may contribute to the pathogenesis of autoimmune diseases. Intraepithelial lymphocytes represent a substantial fraction of gut-associated lymphocytes, but...
Islet cell autoimmunity and transplantation tolerance: two distinct mechanisms (2003)
Pearson, Todd, Markees, Thomas G., Serreze, David V., Pierce, Melissa A., Wicker, Linda S., Peterson, Laurence B., ...
Recent advances in islet transplantation have enabled physicians to cure type 1 autoimmune diabetes, but at the cost of lifelong immunosuppression with its attendant side effects and long-term health...
Turgeon, Nicole A., Banuelos, Scott J., Shultz, Leonard D., Lyons, Bonnie L., Iwakoshi, Neal N., Greiner, Dale L., ...
Small animal models with the capacity to support engraftment of a functional human immune system are needed to facilitate studies of human alloimmunity. In the present investigation, non-obese...
Genetic separation of the transplantation tolerance and autoimmune phenotypes in NOD mice (2003)
Pearson, Todd, Markees, Thomas G., Serreze, David V., Pierce, Melissa A., Wicker, Linda S., Peterson, Laurence B., ...
Seung, Edward, Mordes, John P., Rossini, Aldo A., Greiner, Dale L.
Allogeneic hematopoietic chimerism leading to central tolerance has significant therapeutic potential. Realization of that potential has been impeded by the need for myeloablative conditioning of the...
Ian4 is required for mitochondrial integrity and T cell survival (2003)
Pandarpurkar, Malini, Wilson-Fritch, Leanne, Corvera, Silvia, Markholst, Helle, Hornum, Lars, Greiner, Dale L., ...
Apoptosis is a regulated cell death program controlled by extrinsic and intrinsic signaling pathways. The intrinsic pathway involves stress signals that activate pro-apoptotic members of the Bcl-2...
Induction of tolerance for islet transplantation for type 1 diabetes (2003)
Seung, Edward, Mordes, John P., Greiner, Dale L., Rossini, Aldo A.
Type 1 diabetes is an autoimmune disorder characterized by selective destruction of pancreatic b cells and absolute insulin deficiency. Even when treated well, control is imperfect and complications...
Pearson, Todd, Markees, Thomas G., Serreze, David V., Pierce, Melissa A., Marron, Michele P., Wicker, Linda S., ...
Curing type 1 diabetes by islet transplantation requires overcoming both allorejection and recurrent autoimmunity. This has been achieved with systemic immunosuppression, but tolerance induction...
Infections that induce autoimmune diabetes in BBDR rats modulate CD4+CD25+ T cell populations (2003)
Zipris, Danny, Hillebrands, Jan-Luuk, Welsh, Raymond M., Rozing, Jan, Xie, Jenny X., Mordes, John P., ...
Viruses are believed to contribute to the pathogenesis of autoimmune type 1A diabetes in humans. This pathogenic process can be modeled in the BBDR rat, which develops pancreatic insulitis and type...
Phillips, Nancy E., Markees, Thomas G., Mordes, John P., Greiner, Dale L., Rossini, Aldo A.
Treatment of mice with a single donor-specific transfusion (DST) plus a brief course of anti-CD154 mAb to block CD40-mediated signaling uniformly induces donor-specific transplantation tolerance....
Pearson, Todd, Markees, Thomas G., Wicker, Linda S., Serreze, David V., Peterson, Laurence B., Mordes, John P., ...
The loss of self-tolerance leading to autoimmune type 1 diabetes in the NOD mouse model involves at least 19 genetic loci. In addition to their genetic defects in self-tolerance, NOD mice resist...
The iddm4 locus segregates with diabetes susceptibility in congenic WF.iddm4 rats (2002)
Mordes, John P., Leif, Jean H., Novak, Stephen, DeScipio, Cheryl, Greiner, Dale L., Blankenhorn, Elizabeth P.
Viral antibody-free BBDR and WF rats never develop spontaneous diabetes. BBDR rats, however, develop autoimmune diabetes after perturbation of the immune system, e.g., by viral infection. We...
Forman, Daron, Welsh, Raymond M., Markees, Thomas G., Woda, Bruce A., Mordes, John P., Rossini, Aldo A., ...
Tolerance-based stem cell transplantation using sublethal conditioning is being considered for the treatment of human disease, but safety and efficacy remain to be established. We have shown that...
Skin allograft maintenance in a new synchimeric model system of tolerance (2001)
Iwakoshi, Neal N., Markees, Thomas G., Turgeon, Nicole A., Thornley, Thomas B., Cuthbert, Amy, Leif, Jean, ...
Treatment of mice with a single donor-specific transfusion plus a brief course of anti-CD154 mAb uniformly induces donor-specific transplantation tolerance characterized by the deletion of...
Bortell, Rita, Waite, Debra J., Whalen, Barbara J., Todd, Derrick James, Leif, Jean H., Lesma, Elena, ...
ART2a and ART2b are isoenzymes expressed on the surface of mature T cells and intraepithelial lymphocytes (IELs) in the rat. They exhibit both adenosine diphosphoribosyltransferase and nicotine...
Todd, Derrick James, Greiner, Dale L., Rossini, Aldo A., Mordes, John P., Bortell, Rita
The intestinal lymphoid compartment of the rat is large and diverse, but the phenotype and functions of its constituent cell populations are not fully characterized. Using new methodology for the...
Requirement of the JIP1 scaffold protein for stress-induced JNK activation (2001)
Whitmarsh, Alan J., Kuan, Chia-Yi, Kennedy, Norman J., Kelkar, Nyaya, Haydar, Tarik F., Mordes, John P., ...
The c-Jun N-terminal kinase (JNK) signal transduction pathway is activated in response to the exposure of cells to environmental stress. Components of the JNK signaling pathway interact with the JIP1...
Bortell, Rita, Moss, Joel, McKenna, Robert C., Rigby, Mark R., Niedzwiecki, Dena, Stevens, Linda A., ...
The presence of NAD-metabolizing enzymes (e.g., ADP-ribosyltransferase (ART)2) on the surface of immune cells suggests a potential immunomodulatory activity for ecto-NAD or its metabolites at sites...
Whalen, Barbara J., Marounek, Jan, Weiser, Peter, Appel, Michael C., Greiner, Dale L., Mordes, John P., ...
Thymocytes from adult BB rats can adoptively transfer autoimmune diabetes to athymic recipients. It is also known that the development of BB rat T-cells is recapitulated in adult thymus organ...
Requirement of the JIP1 scaffold protein for stress-induced JNK activation (2001)
Whitmarsh, Alan J., Kuan, Chia-Yi, Kennedy, Norman J., Kelkar, Nyaya, Haydar, Tarik F., Mordes, John P., ...
Viral infection abrogates CD8(+) T-cell deletion induced by costimulation blockade (2000)
Turgeon, Nicole A., Iwakoshi, Neal N., Phillips, Nancy E., Meyers, William C., Welsh, Raymond M., Greiner, Dale L., ...
BACKGROUND: Treatment with a single donor-specific transfusion (DST) plus a brief course of anti-CD154 monoclonal antibody (mAb) prolongs skin allograft survival in mice. It is known that...
Seung, Edward, Iwakoshi, Neal N., Woda, Bruce A., Markees, Thomas G., Mordes, John P., Rossini, Aldo A., ...
We describe a tolerance-based stem cell transplantation protocol that combines sublethal radiation with transient blockade of the CD40-CD154 costimulatory pathway using an anti-CD154 antibody. With...
Welsh, Raymond M., Markees, Thomas G., Woda, Bruce A., Daniels, Keith A., Brehm, Michael A., Mordes, John P., ...
Treatment with a 2-week course of anti-CD154 antibody and a single transfusion of donor leukocytes (a donor-specific transfusion or DST) permits skin allografts to survive for >100 days in...
Iwakoshi, Neal N., Mordes, John P., Markees, Thomas G., Phillips, Nancy E., Rossini, Aldo A., Greiner, Dale L.
A two-element protocol consisting of one donor-specific transfusion (DST) plus a brief course of anti-CD154 mAb greatly prolongs the survival of murine islet, skin, and cardiac allografts. To study...
Diabetes prone BB rats are severely deficient in natural killer T cells (1999)
Iwakoshi, Neal N., Greiner, Dale L., Rossini, Aldo A., Mordes, John P.
Diabetes prone (DP) BB rats develop spontaneous autoimmune hyperglycemia. Coisogenic diabetes resistant (DR) BB rats develop diabetes in response to immunological and environmental perturbants, but...
A new isolation method for rat intraepithelial lymphocytes (1999)
Todd, Derrick James, Singh, Amrik J., Greiner, Dale L., Mordes, John P., Rossini, Aldo A., Bortell, Rita
Intraepithelial lymphocytes (IELs) play critical roles in gut immunity. In mice, gammadelta T cells are a large component of the IEL population. In the rat, gammadelta IELs are reportedly much less...
NOD mice have a generalized defect in their response to transplantation tolerance induction (1999)
Markees, Thomas G., Serreze, David V., Phillips, Nancy E., Sorli, Christopher H., Gordon, Ethel J., Shultz, Leonard D., ...
A protocol consisting of a single donor-specific transfusion (DST) plus a brief course of anti-CD154 monoclonal antibody (anti-CD40 ligand mAb) induces permanent islet allograft survival in...
Induction of immunologic tolerance for transplantation (1999)
Rossini, Aldo A., Greiner, Dale L., Mordes, John P.
In the second half of the 20th century, the transplantation of replacement organs and tissues to cure disease has become a clinical reality. Success has been achieved as a direct result of progress...
Iwakoshi, Neal N., Goldschneider, Irving, Tausche, Frances, Mordes, John P., Rossini, Aldo A., Greiner, Dale L.
Diabetes-prone (DP) BioBreeding (BB) rats develop spontaneous autoimmune diabetes. DP-BB thymocyte export is reduced, and most thymic emigrants disappear rapidly from peripheral lymphoid tissues....
Markees, Thomas G., Phillips, Nancy E., Gordon, Ethel J., Noelle, Randolph J., Shultz, Leonard D., Mordes, John P., ...
Treatment of C57BL/6 mice with one transfusion of BALB/c spleen cells and anti-CD154 (anti-CD40-ligand) antibody permits BALB/c islet grafts to survive indefinitely and BALB/c skin grafts to survive...
Bortell, Rita, Rigby, Mark R., Stevens, Linda A., Moss, Joel, Kanaitsuka, Toshihiro, Mordes, John P., ...
We report that rat RT6.2 and recombinant mouse Rt6 locus 1 proteins possess auto-ADP-ribosyltransferase activity and that Rt6, but not RT6, catalyzes the ADP-ribosylation of exogenous histones. Based...
The T cell marker RT6 in a rat model of autoimmune diabetes (1997)
Greiner, Dale L., Malkani, Samir, Kanaitsuka, Toshihiro, Bortell, Rita, Doukas, John, Rigby, Mark R., ...
Rigby, Mark R., Bortell, Rita, Greiner, Dale L., Czech, Michael P., Klarlund, Jes K., Mordes, John P., ...
RT6 is a glycosyl-phosphatidylinositol-linked surface molecule present on most mature rat T-cells. RT6+ T-cells can prevent the expression of autoimmune diabetes in the BB rat, but the mechanism is...
The BB/Wor rat and the balance hypothesis of autoimmunity (1996)
Mordes, John P., Bortell, Rita, Doukas, John, Rigby, Mark R., Whalen, Barbara J., Zipris, Danny, ...
Waite, Debra J., Appel, Michael C., Handler, Eugene S., Mordes, John P., Rossini, Aldo A., Greiner, Dale L.
RT6 is a cell surface alloantigen that identifies a regulatory subset of peripheral T cells in the rat. Diabetes-prone BB rats are deficient in peripheral RT6+ T cells and develop spontaneous...
Rigby, Mark R., Bortell, Rita, Stevens, Linda A., Moss, Joel, Kanaitsuka, Toshihiro, Shigeta, Hirofumi, ...
RT6 is a glycosylphosphatidylinositol-linked protein found on the surface of mature rat T lymphocytes. Cells that express RT6 have an immunoregulatory function and modulate the expression of...
Parker, David C., Greiner, Dale L., Phillips, Nancy E., Appel, Michael C., Steele, Alan W., Durie, Fiona H., ...
Combined treatment with allogeneic small lymphocytes or T-depleted small lymphocytes plus a blocking antibody to CD40 ligand (CD40L) permitted indefinite pancreatic islet allograft survival in 37 of...
Thymic epithelial defects and predisposition to autoimmune disease in BB rats (1994)
Doukas, John, Mordes, John P., Swymer, Christine, Niedzwiecki, Dena, Mason, Rebecca, Rozing, Jan, ...
We report an association between thymic epithelial defects and predisposition to autoimmunity. Diabetes-prone (DP) BB rats develop spontaneous hyperglycemia and are deficient in T cell subsets...
Polyinosinic:polycytidylic acid is a potent activator of endothelial cells (1994)
Doukas, John, Cutler, Anne H., Mordes, John P.
Polyinosinic:polycytidylic acid (poly I:C) is a synthetic double-stranded polyribonucleotide that elicits immune responses analogous to those observed during viral infection. It is also known to...
Tafuri, Anna, Bowers, William E., Handler, Eugene S., Appel, Michael C., Lew, Robert A., Greiner, Dale L., ...
Dendritic cells (DC) present antigen and initiate T cell-mediated immune responses. To investigate the possible association of autoimmunity with DC function, we compared the accessory activity of...
Adoptive transfer of autoimmune diabetes and thyroiditis to athymic rats (1990)
McKeever, Una, Mordes, John P., Greiner, Dale L., Appel, Michael C., Rozing, Jan, Handler, Eugene S., ...
We describe the induction of autoimmune diabetes, insulitis, and thyroiditis in athymic rats following injections of major histocompatibility complex compatible spleen cells. Lymphocytes with these...
Welsh, Raymond M., Markees, Thomas G., Woda, Bruce A., Daniels, Keith A., Brehm, Michael A., Mordes, John P., ...
Treatment with a 2-week course of anti-CD154 antibody and a single transfusion of donor leukocytes (a donor-specific transfusion or DST) permits skin allografts to survive for >100 days in...
Seung, Edward, Mordes, John P., Rossini, Aldo A., Greiner, Dale L.
Allogeneic hematopoietic chimerism leading to central tolerance has significant therapeutic potential. Realization of that potential has been impeded by the need for myeloablative conditioning of the...
Ian4 is required for mitochondrial integrity and T cell survival
Pandarpurkar, Malini, Wilson-Fritch, Leanne, Corvera, Silvia, Markholst, Helle, Hornum, Lars, Greiner, Dale L., ...
Apoptosis is a regulated cell death program controlled by extrinsic and intrinsic signaling pathways. The intrinsic pathway involves stress signals that activate pro-apoptotic members of the Bcl-2...
Mordes, John P., Guberski, Dennis L., Leif, Jean H., Woda, Bruce A., Flanagan, Joan F., Greiner, Dale L., ...
We describe a new rat model of autoimmune diabetes that arose in a major histocompatibility complex (MHC) congenic LEW rat. Spontaneous diabetes in LEW.1WR1 rats (RT1u/u/a) occurs with a cumulative...
Requirement of the JIP1 scaffold protein for stress-induced JNK activation
Whitmarsh, Alan J., Kuan, Chia-Yi, Kennedy, Norman J., Kelkar, Nyaya, Haydar, Tarik F., Mordes, John P., ...
The c-Jun N-terminal kinase (JNK) signal transduction pathway is activated in response to the exposure of cells to environmental stress. Components of the JNK signaling pathway interact with the JIP1...
Welsh, Raymond M., Markees, Thomas G., Woda, Bruce A., Daniels, Keith A., Brehm, Michael A., Mordes, John P., ...
Treatment with a 2-week course of anti-CD154 antibody and a single transfusion of donor leukocytes (a donor-specific transfusion or DST) permits skin allografts to survive for >100 days in...
Seung, Edward, Mordes, John P., Rossini, Aldo A., Greiner, Dale L.
Allogeneic hematopoietic chimerism leading to central tolerance has significant therapeutic potential. Realization of that potential has been impeded by the need for myeloablative conditioning of the...
Ian4 is required for mitochondrial integrity and T cell survival
Pandarpurkar, Malini, Wilson-Fritch, Leanne, Corvera, Silvia, Markholst, Helle, Hornum, Lars, Greiner, Dale L., ...
Apoptosis is a regulated cell death program controlled by extrinsic and intrinsic signaling pathways. The intrinsic pathway involves stress signals that activate pro-apoptotic members of the Bcl-2...
Requirement of the JIP1 scaffold protein for stress-induced JNK activation
Whitmarsh, Alan J., Kuan, Chia-Yi, Kennedy, Norman J., Kelkar, Nyaya, Haydar, Tarik F., Mordes, John P., ...
The c-Jun N-terminal kinase (JNK) signal transduction pathway is activated in response to the exposure of cells to environmental stress. Components of the JNK signaling pathway interact with the JIP1...
CHOP Mediates Endoplasmic Reticulum Stress-Induced Apoptosis in Gimap5-Deficient T Cells
Pino, Steven C., O'Sullivan-Murphy, Bryan, Lidstone, Erich A., Yang, Chaoxing, Lipson, Kathryn L., Jurczyk, Agata, ...
Gimap5 (GTPase of the immunity-associated protein 5) has been linked to the regulation of T cell survival, and polymorphisms in the human GIMAP5 gene associate with autoimmune disorders. The...
Pino, Steven C., O’Sullivan-Murphy, Bryan, Lidstone, Erich A., Thornley, Thomas B., Jurczyk, Agata, Urano, Fumihiko, ...
T cell receptor (TCR) ligation (signal one) in the presence of co-stimulation (signal two) results in downstream signals that increase protein production enabling naïve T cells to fully activate and...