Miller, David M., Thornley, Thomas B., Pearson, Todd, Kruger, Annie Joseph, Yamazaki, Masahiro, Shultz, Leonard D., ...
Activation of TLR4 by administration of LPS shortens the survival of skin allografts in mice treated with costimulation blockade through a CD8 T cell-dependent, MyD88-dependent, and type I IFN...
Mangada, Julie A., Pearson, Todd, Brehm, Michael A., Wicker, Linda S., Peterson, Laurence B., Shultz, Leonard D., ...
OBJECTIVE: NOD mice model human type 1 diabetes and are used to investigate tolerance induction protocols for islet transplantation in a setting of autoimmunity. However, costimulation blockade-based...
Pearson, Todd, Shultz, Leonard D., Miller, David M., King, Marie A., Laning, Joseph, Fodor, William, ...
Immunodeficient hosts engrafted with human lymphohaematopoietic cells hold great promise as a preclinical bridge for understanding human haematopoiesis and immunity. We now describe a new...
Human BLyS facilitates engraftment of human PBL derived B cells in immunodeficient mice (2008)
Schmidt, Madelyn R., Appel, Michael C., Giassi, Lisa J., Greiner, Dale L., Shultz, Leonard D., Woodland, Robert T.
The production of fully immunologically competent humanized mice engrafted with peripheral lymphocyte populations provides a model for in vivo testing of new vaccines, the durability of immunological...
T cell-specific siRNA delivery suppresses HIV-1 infection in humanized mice (2008)
Kumar, Priti D., Ban, Hong-Seok, Kim, Sang-Soo, Wu, Haoquan, Pearson, Todd, Greiner, Dale L., ...
Evaluation of the therapeutic potential of RNAi for HIV infection has been hampered by the challenges of siRNA delivery and lack of suitable animal models. Using a delivery method for T cells, we...
Giassi, Lisa J., Pearson, Todd, Shultz, Leonard D., Laning, Joseph, Biber, Kristin, Kraus, Morey, ...
Umbilical cord blood (UCB) is increasingly being used for human hematopoietic stem cell (HSC) transplantation in children but often requires pooling multiple cords to obtain sufficient numbers for...
Pearson, Todd, Shultz, Leonard D., Lief, J., Burzenski, Lisa M., Gott, Bruce, Chase, T., ...
AIMS/HYPOTHESIS: To develop and validate a new immunodeficient mouse strain that spontaneously develops a non-autoimmune hyperglycaemia to serve as a diabetic host for human islets and human beta...
Creation of "humanized" mice to study human immunity (2008)
Pearson, Todd, Greiner, Dale L., Shultz, Leonard D.
"Humanized" mice are a promising translational model for studying human hematopoiesis and immunity. Their utility has been enhanced by the development of new stocks of immunodeficient hosts, most...
King, Marie A., Pearson, Todd, Shultz, Leonard D., Leif, Jean H., Bottino, Rita, Trucco, Massimo, ...
Immunodeficient NOD-scid mice bearing a targeted mutation in the IL2 receptor common gamma chain (Il2rgamma(null)) readily engraft with human stem cells. Here we analyzed human peripheral blood...
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...
Humanized NOD/LtSz-scid IL2 receptor common gamma chain knockout mice in diabetes research (2007)
Shultz, Leonard D., Pearson, Todd, King, Marie A., Giassi, Lisa J., Carney, Lisa, Gott, Bruce, ...
There are many rodent models of autoimmune diabetes that have been used to study the pathogenesis of human type 1 diabetes (T1D), including the non-obese diabetic (NOD) mouse, the biobreeding (BB)...
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...
Constant rate of steady-state self-antigen trafficking from skin to regional lymph nodes (2006)
Yoshino, Miya, Yamazaki, Hidetoshi, Shultz, Leonard D., Hayashi, Shin-Ichi
It is suggested that dendritic cells (DCs) capture and present both foreign antigens such as components of pathogens as well as endogenous self-antigens. However, the magnitude of self-antigen...
Constant rate of steady-state self-antigen trafficking from skin to regional lymph nodes (2006)
Yoshino, Miya, Yamazaki, Hidetoshi, Shultz, Leonard D., Hayashi, Shin-Ichi
It is suggested that dendritic cells (DCs) capture and present both foreign antigens such as components of pathogens as well as endogenous self-antigens. However, the magnitude of self-antigen...
Jaeschke, Anja, Rincon, Mercedes, Doran, Beth, Reilly, Judith, Neuberg, Donna S., Greiner, Dale L., ...
The c-Jun NH(2)-terminal kinase isoform (JNK) 1 is implicated in type 2 diabetes. However, a potential role for the JNK2 protein kinase in diabetes has not been established. Here, we demonstrate that...
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...
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...
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...
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., ...
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...
Kentaro Kikuchi, Zhe-Xiong Lian, Xiao-Song He, Aftab A. Ansari, Miyuki Ishibashi, Hiroshi Miyakawa, ...
Relatively little is known for the differentiation and maturation process of human B cells to plasma cells. This is particularly important in reconstitution work involving transfer of autoantibodies....
Kentaro Kikuchi, Zhe-Xiong Lian, Xiao-Song He, Aftab A. Ansari, Miyuki Ishibashi, Hiroshi Miyakawa, ...
Relatively little is known for the differentiation and maturation process of human B cells to plasma cells. This is particularly important in reconstitution work involving transfer of autoantibodies....
Zhe-Xiong Lian, Hiroto Kita, Tomoyuki Okada, Tom Hsu, Leonard D. Shultz, Kenneth Dorshkind, ...
Reductions in populations of both Pre-B cell (Hardy fractions D) and Pro-B cells (Hardy fractions B–C) have been described in association with murine lupus. Recent studies of B cell populations,...
Wagar, Eric J., Cromwell, Mary A., Shultz, Leonard D., Woda, Bruce A., Sullivan, John L., Hesselton, RuthAnn M., ...
Human PBMC engraft in mice homozygous for the severe combined immunodeficiency (Prkdcscid) mutation (Hu-PBL-scid mice). Hu-PBL-NOD-scid mice generate 5- to 10-fold higher levels of human cells than...
Shultz, Leonard D., Lang, Pamela A., Christianson, Sherri W., Gott, Bruce, Lyons, Bonnie L., Umeda, Syuji, ...
Development of a small animal model for the in vivo study of human immunity and infectious disease remains an important goal, particularly for investigations of HIV vaccine development. NOD/Lt mice...
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...
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...
SCID mouse models of human stem cell engraftment (1998)
Greiner, Dale L., Hesselton, RuthAnn M., Shultz, Leonard D.
The discovery of the severe combined immunodeficiency (scid) mouse mutation has provided a tool for establishment of small animal models as hosts for the in vivo analysis of normal and malignant...
Blockade of CD40-CD154 interferes with human T cell engraftment in scid mice (1998)
Foy, Teresa M., McIlraith, Melissa, Masters, Sally R., Dunn, Jonathan J., Rossini, Aldo A., Shultz, Leonard D., ...
Antibodies to the ligand for CD40 (CD154) have been shown to exert profound effects on the development of cell-mediated immune responses in mice. The present study shows that an antibody to human...
Enhanced human CD4+ T cell engraftment in beta2-microglobulin-deficient NOD-scid mice (1997)
Christianson, Sherri W., Greiner, Dale L., Hesselton, RuthAnn M., Leif, Jean H., Wagar, Eric James, Schweitzer, Isabelle B., ...
Genetic crosses produced NOD/LtSz mice doubly homozygous for the severe combined immunodeficiency (scid) mutation and the beta2m (B2m) null allele. Both NOD/LtSz-scid/scid and NOD/LtSz-scid/scid...
Yuichi Takeoka, Shao-Yuan Chen, Richard L. Boyd, Koichi Tsuneyama, Nobuhisa Taguchi, Shinji Morita, ...
It is widely accepted that the thymic microenvironment regulates normal thymopoiesis through a highly coordinated and complex series of cellular and cytokine interactions. A direct corollary of this...
Larochelle, André, Vormoor, Josef, Lapidot, Tsvee, Sher, Graham, Furukawa, Tatsuo, Li, Qiliang, ...
Permanent correction of genetic deficiencies of the hematopoietic system requires gene transfer into stem cells and long-term lineage specific expression after autologous transplantation. However,...
Szomolanyi-Tsuda, Eva, Dundon, Patricia L., Joris, Isabelle, Shultz, Leonard D., Woda, Bruce A., Welsh, R M
Infection of severe combined immunodeficient mice, which lack T and B lymphocytes, with polyomavirus (PyV) induced an acute hematological disorder leading to the death of the mice by 2 weeks...
Sandra M. Hayes, Leonard D. Shultz, Dale L. Greiner
Mice homozygous for the viable motheaten (meυ) allele manifest abnormalities in thymocytopoiesis, are severely immunodeficient, and develop autoimmune disorders early in life. Premature thymic...
T. V. Rajan, Leonard D. Shultz
The mechanism by which the antigen-specific immune system distinguishes between foreign antigens (toward which it mounts an immune response) and self-antigens (of which it is tolerant) is not...
Noben-Trauth, Nancy, Shultz, Leonard D., Brombacher, Frank, Urban, Joseph F., Gu, Hua, Paul, William E.
IL-4 receptor α chain (IL-4Rα)-deficient mice were generated by gene-targeting in BALB/c embryonic stem cells. Mutant mice showed a loss of IL-4 signal transduction and functional activity. The...
Immunity in Experimental Murine Filariasis: Roles of T and B Cells Revisited
Babu, Subash, Shultz, Leonard D., Klei, Thomas R., Rajan, T. V.
We have reevaluated the contributions of T and B cells in Brugia malayi infection by utilizing knockout mice on a uniform background (C57BL/6J). We find that B-cell-deficient mice are more permissive...
Babu, Subash, Ganley, Lisa M., Klei, Thomas R., Shultz, Leonard D., Rajan, T. V.
We have investigated the roles of gamma interferon (IFN-γ) and interleukin-4 (IL-4) in host defense against Brugia malayi. Our data suggest that the lack of either IFN-γ or IL-4 prolongs the time...
Paciorkowski, Natalia, Shultz, Leonard D., Rajan, T. V.
Lymphatic filariasis is a tropical disease caused by the nematode parasites Wuchereria bancrofti and Brugia malayi. Whereas the protective potential of T lymphocytes in filarial infection is well...
Nguyen, Vu Thuong, Ndoye, Assane, Shultz, Leonard D., Pittelkow, Mark R., Grando, Sergei A.
Pemphigus is an autoimmune disease of skin adhesion associated with autoantibodies against a number of keratinocyte antigens, such as the adhesion molecules desmoglein (Dsg) 1 and 3 and acetylcholine...
Cytotoxicity of Rabbit Blood for Listeria monocytogenes
Shultz, Leonard D., Wilder, M. S.
Our studies reveal that normal rabbit blood contains a potent bactericidin active against Listeria monocytogenes. The factor is present in greatest amounts in fresh undiluted serum but is absent in...
Fate of Listeria monocytogenes in Normal Rabbit Serum
Shultz, Leonard D., Wilder, Martin S.
Viability of Listeria monocytogenes suspended in either normal rabbit serum or listericidal factor is significantly reduced before cell lysis. In normal serum Listeria populations are initially...
Jaeschke, Anja, Rincón, Mercedes, Doran, Beth, Reilly, Judith, Neuberg, Donna, Greiner, Dale L., ...
The c-Jun NH2-terminal kinase isoform (JNK) 1 is implicated in type 2 diabetes. However, a potential role for the JNK2 protein kinase in diabetes has not been established. Here, we demonstrate that...
Noben-Trauth, Nancy, Shultz, Leonard D., Brombacher, Frank, Urban, Joseph F., Gu, Hua, Paul, William E.
IL-4 receptor α chain (IL-4Rα)-deficient mice were generated by gene-targeting in BALB/c embryonic stem cells. Mutant mice showed a loss of IL-4 signal transduction and functional activity. The...
Immunity in Experimental Murine Filariasis: Roles of T and B Cells Revisited
Babu, Subash, Shultz, Leonard D., Klei, Thomas R., Rajan, T. V.
We have reevaluated the contributions of T and B cells in Brugia malayi infection by utilizing knockout mice on a uniform background (C57BL/6J). We find that B-cell-deficient mice are more permissive...
Babu, Subash, Ganley, Lisa M., Klei, Thomas R., Shultz, Leonard D., Rajan, T. V.
We have investigated the roles of gamma interferon (IFN-γ) and interleukin-4 (IL-4) in host defense against Brugia malayi. Our data suggest that the lack of either IFN-γ or IL-4 prolongs the time...
Paciorkowski, Natalia, Shultz, Leonard D., Rajan, T. V.
Lymphatic filariasis is a tropical disease caused by the nematode parasites Wuchereria bancrofti and Brugia malayi. Whereas the protective potential of T lymphocytes in filarial infection is well...
Nguyen, Vu Thuong, Ndoye, Assane, Shultz, Leonard D., Pittelkow, Mark R., Grando, Sergei A.
Pemphigus is an autoimmune disease of skin adhesion associated with autoantibodies against a number of keratinocyte antigens, such as the adhesion molecules desmoglein (Dsg) 1 and 3 and acetylcholine...
Cytotoxicity of Rabbit Blood for Listeria monocytogenes
Shultz, Leonard D., Wilder, M. S.
Our studies reveal that normal rabbit blood contains a potent bactericidin active against Listeria monocytogenes. The factor is present in greatest amounts in fresh undiluted serum but is absent in...
Fate of Listeria monocytogenes in Normal Rabbit Serum
Shultz, Leonard D., Wilder, Martin S.
Viability of Listeria monocytogenes suspended in either normal rabbit serum or listericidal factor is significantly reduced before cell lysis. In normal serum Listeria populations are initially...
Jaeschke, Anja, Rincón, Mercedes, Doran, Beth, Reilly, Judith, Neuberg, Donna, Greiner, Dale L., ...
The c-Jun NH2-terminal kinase isoform (JNK) 1 is implicated in type 2 diabetes. However, a potential role for the JNK2 protein kinase in diabetes has not been established. Here, we demonstrate that...
Greiner, Dale L., Shultz, Leonard D., Yates, Jon, Appel, Michael C., Perdrizet, George, Hesselton, RuthAnn M., ...
T and B lymphocyte-deficient mice homozygous for the severe combined immunodeficiency (SCID) mutation can be immunologically engrafted with human lymphocytes. However, low levels of human peripheral...
Myint, Yi Yi, Miyakawa, Kazuhisa, Naito, Makoto, Shultz, Leonard D, Oike, Yuichi, Yamamura, Ken-ichi, ...
Although young mice homozygous for the osteopetrosis (op) mutation usually developed prominent osteopetrosis, its severity was markedly reduced in aged op/op mice. This age-associated reversal of...
Umeda, Syuji, Beamer, Wesley G., Takagi, Katsumasa, Naito, Makoto, Hayashi, Shin-Ichi, Yonemitsu, Hiroyuki, ...
Mice homozygous for the motheaten (Hcphme) or viable motheaten (Hcphme-v) mutations are deficient in functional SHP-1 protein-tyrosine phosphatase and show severe defects in hematopoiesis. Comparison...
Development of functional human blood and immune systems in NOD/SCID/IL2 receptor γ chainnull mice
Ishikawa, Fumihiko, Yasukawa, Masaki, Lyons, Bonnie, Yoshida, Shuro, Miyamoto, Toshihiro, Yoshimoto, Goichi, ...
Here we report that a new nonobese diabetic/severe combined immunodeficient (NOD/SCID) mouse line harboring a complete null mutation of the common cytokine receptor γ chain (NOD/SCID/interleukin 2...
Humanized mice: are we there yet?
Macchiarini, Francesca, Manz, Markus G., Palucka, A. Karolina, Shultz, Leonard D.
Animal models have been instrumental in increasing the understanding of human physiology, particularly immunity. However, these animal models have been limited by practical considerations and genetic...
Appearance of Human Plasma Cells Following Differentiation of Human B Cells in NOD/SCID Mouse Spleen
Kikuchi, Kentaro, Lian, Zhe-Xiong, He, Xiao-Song, Ansari, Aftab A., Ishibashi, Miyuki, Miyakawa, Hiroshi, ...
Relatively little is known for the differentiation and maturation process of human B cells to plasma cells. This is particularly important in reconstitution work involving transfer of autoantibodies....
Hayes, Sandra M., Shultz, Leonard D., Greiner, Dale L.
Mice homozygous for the viable motheaten (meυ) allele manifest abnormalities in thymocytopoiesis, are severely immunodeficient, and develop autoimmune disorders early in life. Premature thymic...
Rajan, T. V., Shultz, Leonard D., Greinert, Dale L.
The mechanism by which the antigen-specific immune system distinguishes between foreign antigens (toward which it mounts an immune response) and self-antigens (of which it is tolerant) is not...
Takeoka, Yuichi, Chen, Shao-Yuan, Boyd, Richard L., Tsuneyama, Koichi, Taguchi, Nobuhisa, Morita, Shinji, ...
It is widely accepted that the thymic microenvironment regulates normal thymopoiesis through a highly coordinated and complex series of cellular and cytokine interactions. A direct corollary of this...
Lian, Zhe-Xiong, Kita, Hiroto, Okada, Tomoyuki, Hsu, Tom, Shultz, Leonard D., Dorshkind, Kenneth, ...
Reductions in populations of both Pre-B cell (Hardy fractions D) and Pro-B cells (Hardy fractions B–C) have been described in association with murine lupus. Recent studies of B cell populations,...
B1 B Lymphocytes Play a Critical Role in Host Protection against Lymphatic Filarial Parasites
Paciorkowski, Natalia, Porte, Patricia, Shultz, Leonard D., Rajan, T.V.
Host defense against multicellular, extracellular pathogens such as nematode parasites is believed to be mediated largely, if not exclusively, by T lymphocytes. During our investigations into the...
Nakamura, Mary C., Niemi, Eréne C., Fisher, Mark J., Shultz, Leonard D., Seaman, William E., Ryan, James C.
The lytic activity of natural killer (NK) cells is inhibited by the expression of class I major histocompatibility complex (MHC) antigens on target cells. In murine NK cells, Ly-49A mediates...
Appearance of Human Plasma Cells Following Differentiation of Human B Cells in NOD/SCID Mouse Spleen
Kikuchi, Kentaro, Lian, Zhe-Xiong, He, Xiao-Song, Ansari, Aftab A., Ishibashi, Miyuki, Miyakawa, Hiroshi, ...
Relatively little is known for the differentiation and maturation process of human B cells to plasma cells. This is particularly important in reconstitution work involving transfer of autoantibodies....
Human BLyS Facilitates Engraftment of Human PBL Derived B Cells in Immunodeficient Mice
Schmidt, Madelyn R., Appel, Michael C., Giassi, Lisa J., Greiner, Dale L., Shultz, Leonard D., Woodland, Robert T.
The production of fully immunologically competent humanized mice engrafted with peripheral lymphocyte populations provides a model for in vivo testing of new vaccines, the durability of immunological...
Ishikawa, Fumihiko, Niiro, Hiroaki, Iino, Tadafumi, Yoshida, Shuro, Saito, Noriyuki, Onohara, Shinya, ...
Two distinct dendritic cell (DC) subsets, conventional DCs (cDCs) and plasmacytoid DCs (pDCs), have been shown to develop via either the myeloid or the lymphoid pathway in murine hematopoiesis....
Croker, Ben A., Lawson, Brian R., Berger, Michael, Eidenschenk, Celine, Blasius, Amanda L., Moresco, Eva Marie Y., ...
A recessive phenotype called spin (spontaneous inflammation) was induced by N-ethyl-N-nitrosourea (ENU) mutagenesis in C57BL/6J mice. Homozygotes display chronic inflammatory lesions affecting the...