A5069767496- T-cell and B-cell Immunology
- Immune Cell Function and Interaction
- Immunotherapy and Immune Responses
- Ion channel regulation and function
- interferon and immune responses
- Cytokine Signaling Pathways and Interactions
- CAR-T cell therapy research
- Atherosclerosis and Cardiovascular Diseases
- Cancer Immunotherapy and Biomarkers
- Diabetes and associated disorders
- IL-33, ST2, and ILC Pathways
- Library Science and Administration
- Herpesvirus Infections and Treatments
- Epigenetics and DNA Methylation
- Cellular Mechanics and Interactions
- Mast cells and histamine
- Muscle Physiology and Disorders
- Circadian rhythm and melatonin
- HIV Research and Treatment
- Complement system in diseases
- Acute Myeloid Leukemia Research
- Reproductive System and Pregnancy
- Genetic Neurodegenerative Diseases
- Cell Adhesion Molecules Research
- Pancreatic function and diabetes
National Institute of Allergy and Infectious Diseases
2011-2023
National Institutes of Health
2011-2023
Office of Extramural Research
2014-2015
Rutgers, The State University of New Jersey
2006-2011
Johnson University
2007-2011
Kennesaw State University
2008
Molina Center for Energy and the Environment
2007
University of Alabama
2000
Eunice Kennedy Shriver National Institute of Child Health and Human Development
1992-1996
Peripheral tolerance may be maintained by a population of regulatory/suppressor T cells that prevent the activation autoreactive recognizing tissue-specific antigens. We have previously shown CD4+CD25+ represent unique suppressor can both initiation organ-specific autoimmune disease after day 3 thymectomy and effector function cloned autoantigen-specific CD4+ cells. To analyze mechanism action these cells, we established an in vitro model system mimics vivo. Purified failed to proliferate...
Helios, a member of the Ikaros transcription factor family, is preferentially expressed at mRNA level by regulatory T cells (Treg cells). We evaluated Helios protein expression using newly generated mAb and demonstrated that it in all thymocytes double negative 2 stage thymic development. Although was 100% CD4(+)CD8(-)Foxp3(+) thymocytes, its peripheral lymphoid tissues restricted to subpopulation ( approximately 70%) Foxp3(+) mice humans. Neither mouse nor human naive induced express Foxp3...
Abstract CD4+CD25+ T cells represent a unique population of “professional” suppressor that prevent induction organ-specific autoimmune disease. In vitro, were anergic to simulation via the TCR and when cultured with CD4+CD25− cells, markedly suppressed polyclonal cell proliferation by specifically inhibiting production IL-2. Suppression was cytokine independent, contact dependent, required activation suppressors their TCR. Further characterization demonstrated they do not contain memory or...
Thymectomy of susceptible strains mice on day 3 life results in a spectrum organ-specific autoimmunity that can be prevented by reconstitution the thymectomized animals early with normal adult lymphocytes. The effectors and suppressors this model have been convincingly shown to CD4+ T cells. It has demonstrated recently regulatory cells prevent disease coexpress CD25. We further characterized population CD4+CD25+ immunoregulatory they suppress not only induction post-thymectomy, but also...
CD4(+)CD25(+) regulatory T cells inhibit organ-specific autoimmune diseases induced by CD4(+)CD25(-) and are potent suppressors of cell activation in vitro. Their mechanism suppression remains unknown, but most vitro studies suggest that it is contact-dependent cytokine independent. The role TGF-beta1 suppressor function unclear. While have failed to reverse with anti-transforming growth factor (TGF)-beta1 vitro, one recent study has reported express surface can be completely abrogated high...
CD4(+)CD25(+) T cells are potent immunoregulatory that suppress TCR-induced proliferation of CD4 and CD8 in vitro by a cell contact-dependent mechanism. Addition IL-2 or anti-CD28 abrogates CD4(+)CD25(+)-mediated suppression has been assumed to "break suppression." We examined mRNA quantitative PCR cocultures mouse CD4(+)CD25(-) cells. Although gene transcription was inhibited the presence absence exogenous IL-2, addition stimulated endogenous production. Surprisingly, also restored...
Abstract The transcription factor Helios is expressed in a large subset of Foxp3 + Tregs. We previously proposed that marker thymic derived Treg (tTreg), while − were induced from T conventional (Tconv) cells the periphery (pTreg). To compare two subpopulations, we generated Helios‐GFP reporter mice and crossed them to Foxp3‐RFP mice. population more activated phenotype, had slightly higher suppressive capacity vitro highly demethylated TSDR but equivalent their ability suppress inflammatory...
The in vivo differentiation/survival of CD4(+)CD25(+) T suppressor cells is dependent on IL-2 and CD28-mediated costimulatory signals. To determine the cytokine requirements for CD25(+) vitro, we established a two-stage culture system where were activated primary culture. In subsequent culture, then mixed with responders order to assess their function. Pre-culture anti-CD3 alone resulted poor survival minimal induction activity. presence or IL-4, but not IL-6, IL-7, IL-9, IL-10 IL-15,...
Abstract A subpopulation (60–70%) of Foxp3+ regulatory T cells (Tregs) in both mouse and man expresses the transcription factor Helios, but its role Treg function is still unknown. We generated Treg-specific Helios-deficient mice to examine Helios Tregs. show that selective deletion Tregs leads slow, progressive systemic immune activation, hypergammaglobulinemia, enhanced germinal center formation absence organ-specific autoimmunity. suppressor was normal vitro, as well an vivo inflammatory...
Two families of transcription factors mediate interferon (IFN) signaling. The first family, signal transducers and activators (STATs), is activated within minutes IFN treatment. Specific phosphorylation events lead to their translocation the nucleus, formation transcriptional complexes, induction second family termed regulatory (IRFs). Interferon consensus sequence binding protein (ICSBP) a member IRF that expressed only in cells immune system acts as repressor. ICSBP binds DNA through...
Treg cells express high levels of the glucocorticoid-induced tumor necrosis factor-related receptor (GITR), while resting conventional T (Tconv) low that are increased upon activation. Manipulation GITR/GITR-Ligand (GITR-L) interactions results in enhancement immune responses, but it remains unclear whether this is secondary to costimulation Tconv or reversal Treg-cell-mediated suppression. Here, we used a nondepleting Fc-GITR-L and combinations WT GITR KO reexamine effects stimulation on...
Activated T regulatory cells (Tregs) express latent TGF-β1 on their cell surface bound to GARP. Although integrins have been implicated in mediating the release of active from complex and binding protein, role processing TGF-β1/GARP is unclear. Mouse CD4(+)Foxp3(+) Treg, but not CD4(+)Foxp3(-) cells, expressed integrin β8 (Itgb8) as detected by quantitative RT-PCR. Itgb8 expression was a marker thymically derived (t)Treg, because it could be Foxp3(+)Helios(-) Tregs or Foxp3(+) induced vitro....
Interferon consensus sequence binding protein (ICSBP) is a transcription factor of the IFN regulatory (IRF) family. Evidence indicates that this family has function in immune system. Unlike other members family, ICSBP expressed exclusively In work, immunoblot analysis was performed to study expression and various murine lymphocytes. The results show all IRF are constitutively B cells throughout development, resting activated cells. contrast, undetectable thymocytes T cells, while proteins...