A5023002972- Immune Cell Function and Interaction
- T-cell and B-cell Immunology
- Immunotherapy and Immune Responses
- Diabetes and associated disorders
- IL-33, ST2, and ILC Pathways
- CAR-T cell therapy research
- Monoclonal and Polyclonal Antibodies Research
- Pancreatic function and diabetes
- Autoimmune and Inflammatory Disorders Research
- Immune Response and Inflammation
- Cytomegalovirus and herpesvirus research
- Eosinophilic Esophagitis
- vaccines and immunoinformatics approaches
- Transgenic Plants and Applications
- Gut microbiota and health
- Diabetes Management and Research
- Clostridium difficile and Clostridium perfringens research
- Immunodeficiency and Autoimmune Disorders
- Toxin Mechanisms and Immunotoxins
- Vascular Tumors and Angiosarcomas
- Carbohydrate Chemistry and Synthesis
- RNA Interference and Gene Delivery
- Lymphoma Diagnosis and Treatment
- Galectins and Cancer Biology
- T-cell and Retrovirus Studies
University of Chicago
2015-2025
Howard Hughes Medical Institute
2006-2016
Pulmonary and Critical Care Associates
2011
Brigham Young University
2002-2006
Scripps Research Institute
2002-2004
National Institute of Diabetes and Digestive and Kidney Diseases
2004
University of Gothenburg
2004
Princeton University
1995-2003
National Institutes of Health
1991-2003
National Institute of Dental and Craniofacial Research
2003
The mouse thymus contains a mature T cell subset that is distinguishable from the mainstream thymocytes by several characteristics. It restricted in its usage of receptor (TCR) V beta genes to 8, 7, and 2. Its surface phenotype activated/memory cells. carries natural killer NK1.1 marker. Furthermore, though it consists entirely CD4+ CD4-8- cells, selection depends solely upon major histocompatibility complex (MHC) class I expression cells hematopoietic origin. Forced persistence CD8, fact,...
NKT cells represent a distinct lineage of T that coexpress conserved alphabeta cell receptor (TCR) and natural killer (NK) receptors. Although the TCR is characteristically autoreactive to CD1d, lipid-presenting molecule, endogenous ligands for these have not been identified. We show lysosomal glycosphingolipid previously unknown function, isoglobotrihexosylceramide (iGb3), recognized both by mouse human cells. Impaired generation iGb3 in mice lacking beta-hexosaminidase b results severe...
Rare major histocompatibility complex (MHC) class I-like CD1-specific T cells have been isolated from human blood, but it has not determined whether these clones are part of a defined subset selected during cell development, or their recognition CD1 is fortuitous cross-reaction. In mice, an entire alpha beta thymocytes with unique phenotype was found to be CD1-specific. This particular subset, and its counterpart, provide evidence that general role in selecting interacting specialized cells.
alpha-Galactosylceramide (alpha-GalCer) is a glycolipid with potent antitumor properties that binds to CD1d molecules and activates mouse Valpha14 human Valpha24 NKT cells. Surprisingly, we found that, as early 90 min after alpha-GalCer injection in vivo, NK cells also displayed considerable signs of activation, including IFN-gamma production CD69 induction. activation was not observed RAG- or CD1-deficient mice, it decreased by pretreatment anti-IFN-gamma Abs, suggesting despite its rapid...
We have developed a model of syngeneic adoptive transfer for type I diabetes mellitus NOD mice. This consists in injecting spleen cells from diabetic adult mice into newborn recipients. 50% recipients inoculated with 20 X 10(6) develop within the first 10 wk life, at time when none control littermates yet become diabetic. The earliest successful transfers are observed 3 age, controls do not even exhibit histological changes their pancreas. In addition we shown that: (a) both males and...
We describe here a new subset of T cells, found in humans, mice, and cattle. These cells bear canonical cell receptor (TCR) alpha chain containing hAV7S2 AJ33 humans the homologous AV19-AJ33 mice cattle with CDR3 constant length. are CD4(-)CD8(-) double-negative (DN) three species also CD8alphaalpha humans. In their frequency was approximately 1/10 DN, 1/50 CD8alpha+, 1/6,000 CD4(+) lymphocytes, they display an activated/memory phenotype (CD45RAloCD45RO+). They preferentially use hBV2S1...
CD1d-restricted autoreactive natural killer (NK)T cells have been reported to regulate a range of disease conditions, including type I diabetes and immune rejection cancer, through the secretion either T helper (Th)2 or Th1 cytokines. However, mechanisms underlying Th2 versus cytokine by these are not well understood. Since most healthy subjects express <1 NKT cell per 1,000 peripheral blood lymphocytes (PBLs), we devised new method based on combined used receptor (TCR)-specific...
The CD1 family of major histocompatibility complex (MHC)-like molecules specializes in presenting lipid and glycolipid antigens to α/β T lymphocytes, but little is known about the size CD1-restricted cell population or frequency lymphocytes specific for a given antigen. Here, we report generation use mouse CD1d1–glycolipid tetramers visualize CD1d-restricted cells. In contrast with previous BIAcore-based estimates very short half-lives CD1d–glycolipid complexes, found that dissociation rate...
Mouse NK1+ T cells constitute a subset of alpha/beta TCR+ that specialize in the rapid production cytokines, particular IL-4, and may promote differentiation Th2-type CD4 cells. Their TCRs, like those homologous human cells, use an invariant TCR alpha chain were recently shown to be specific for beta 2-microglobulin-associated, MHC class I-like CD1 molecules, which are encoded outside MHC. In contrast mainstream thymocytes, recognize their positively selecting ligand on thymic epithelial...
CD1d-restricted autoreactive natural killer (NK1.1+) T cells function as regulatory in various disease conditions. Using improved tetramer tracking methodology, we identified a NK1.1- thymic precursor and followed its differentiation emigration to tissues by direct cell transfer situ labeling studies. A major lineage expansion occurred within the thymus after positive selection before NK receptor expression. Surprisingly, cytokine analysis of developmental intermediates between NK+ stages...
Immune responses dominated by interleukin-4 (IL-4)-producing T helper type 2 (TH2) cells or interferon gamma (IFN-gamma)-producing 1 (TH1) express distinctive protection against infection with different pathogens. Interleukin-4 promotes the differentiation of naïve CD4+ into IL-4 producers and suppresses their development IFN-gamma producers. CD1-specific splenic CD4+NK1.1+ cells, a numerically minor population, produced promptly on in vivo stimulation. This cell population was essential for...
To complete their maturation, most immature thymocytes depend on the simultaneous engagement of antigen receptor [alpha beta T cell (TCR)] and CD4 or CD8 coreceptors with major histocompatibility complex class II I ligands, respectively. However, a normal subset mature alpha TCR+ did not follow these rules. These expressed NK1.1 restricted set TCRs that are intrinsically I-reactive because positive selection was I-dependent but CD8-independent. cells were CD4+ CD4-8- never CD8+, presence...
Large quantities of immunoglobulin A (IgA) are constitutively secreted by intestinal plasma cells to coat and contain the commensal microbiota, yet specificity these antibodies remains elusive. Here we profiled reactivities single murine IgA cloning characterizing large numbers monoclonal antibodies. IgAs were not specific individual bacterial taxa but rather polyreactive, with broad reactivity a diverse, defined, subset microbiota. These arose at low frequencies among naïve B selected into...
Progression to destructive insulitis in nonobese diabetic (NOD) mice is linked the failure of regulatory cells, possibly involving T helper type 2 (Th2) cells. Natural killer (NK) cells might be involved diabetes, given their deficiency NOD and prevention diabetes by adoptive transfer α/β double-negative thymocytes. Here, we evaluated role NK using transgenic expressing cell antigen receptor (TCR) α chain Vα14-Jα281 characteristic Precise identification NK1.1+ was based on out-cross with...