The major objective of our studies is to characterize cell surface structures on T and B lymphocytes as well as on non-T accessory cells (AC) which, in addition to the specific antigen receptor, are involved in the process of lymphocyte activation. Over the past 4 years we have developed a number of monoclonal antibodies (Mabs) to mouse T lymphocyte cell surface antigens which are capable of stimulating or inhibiting T cell triggering. One group of these reagents is directed to the receptor for interleukin-2 (IL-2) on activated murine lymphocytes. These Mabs have been used to further characterize the role of non-T AC in the induction of IL-2 receptor expression and to isolate and sequence a cDNA that contains the entire coding region of the murine IL-2 receptor. A new lymphokine, IL-2 inhibitor, which is capable of neutralizing the biologic activity of Il-2 has been characterized and purified to apparent homogeneity. Newly developed Mabs to the Thy-1 antigen were used to demonstrate the critical role of this molecule in signal transduction following transfection of the Thy-1 gene into human cells. Lastly, we have shown that the L3T4 antigen, a marker for a subpopulation of T cells, may play a dual role in T cell function by interacting with target molecules on AC and by subsequently functioning as a signal transmitter to other cell surface molecules on the T cell. The ultimate goals of our studies are to fully understand the regulatory mechanisms that control T cell activation and differentiation. Mabs to lymphocyte surface antigens should prove to be useful tools in these studies and may also prove to be attractive candidates for in vivo therapeutic use in attempts to modulate or abrogate an ongoing immune response.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Intramural Research (Z01)
Project #
1Z01AI000224-04
Application #
4688403
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
4
Fiscal Year
1985
Total Cost
Indirect Cost
Name
Niaid Extramural Activities
Department
Type
DUNS #
City
State
Country
United States
Zip Code
Zhu, Jinfang; Davidson, Todd S; Wei, Gang et al. (2009) Down-regulation of Gfi-1 expression by TGF-beta is important for differentiation of Th17 and CD103+ inducible regulatory T cells. J Exp Med 206:329-41
Huter, Eva N; Stummvoll, Georg H; DiPaolo, Richard J et al. (2009) Pre-differentiated Th1 and Th17 effector T cells in autoimmune gastritis: Ag-specific regulatory T cells are more potent suppressors than polyclonal regulatory T cells. Int Immunopharmacol 9:540-5
Huter, Eva N; Punkosdy, George A; Glass, Deborah D et al. (2008) TGF-beta-induced Foxp3+ regulatory T cells rescue scurfy mice. Eur J Immunol 38:1814-21
Shevach, Ethan M; Tran, Dat Q; Davidson, Todd S et al. (2008) The critical contribution of TGF-beta to the induction of Foxp3 expression and regulatory T cell function. Eur J Immunol 38:915-7
Stummvoll, Georg H; DiPaolo, Richard J; Huter, Eva N et al. (2008) Th1, Th2, and Th17 effector T cell-induced autoimmune gastritis differs in pathological pattern and in susceptibility to suppression by regulatory T cells. J Immunol 181:1908-16
Shevach, Ethan M (2006) From vanilla to 28 flavors: multiple varieties of T regulatory cells. Immunity 25:195-201
Mendel, Itzhak; Shevach, Ethan M (2006) Activated T cells express the OX40 ligand: requirements for induction and costimulatory function. Immunology 117:196-204
Kullberg, Marika C; Hay, Valerie; Cheever, Allen W et al. (2005) TGF-beta1 production by CD4+ CD25+ regulatory T cells is not essential for suppression of intestinal inflammation. Eur J Immunol 35:2886-95
Wang, Helen Y; Peng, Guangyong; Guo, Zhong et al. (2005) Recognition of a new ARTC1 peptide ligand uniquely expressed in tumor cells by antigen-specific CD4+ regulatory T cells. J Immunol 174:2661-70
Brinster, Carine; Shevach, Ethan M (2005) Bone marrow-derived dendritic cells reverse the anergic state of CD4+CD25+ T cells without reversing their suppressive function. J Immunol 175:7332-40

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