During the last several years this laboratory has continued to be intimately involved in the development of human lymphocyte cell separation procedures, human lymphocyte functional assays, T cell cloning strategies, T cell hybridization and the assessment of T cell surface molecules using monoclonal antibodies that together permit precise analysis of human immune responses in vitro. More recently, our laboratory has begun to utilize DNA-mediated transfer of genes encoding human T cell surface molecules to further explore functional properties of human T cells. The thrust of the current proposal is to bring to bear these newer technologies to analyze the relationship of the function of T cell surface molecules to the cellular interactions important in antigen recognition, T cell triggering and immunoregulation. Recent data from our laboratory and others strongly suggest that many if not all of the already defined surface molecules on human T cells, including the T1, T3, T4, T8 and T11 molecules themselves, as well as recently defined activation antigens, serve as critical structures important in lymphocyte function.
Our specific aims are to: (1) further define the heterogeneity of cellular functions contained within the mutually exclusive T4+ and T8+ subsets of mature human T cells. In these studies we will also continue to analyze the T-T, T-B, and T-macrophage cellular imteractions important in the functions of isolated subsets; (2) further define the precise functional role of T4+ and T8+ glycoprotein molecules themselves in antigen recognition and MHC restriction as well as helper and suppressor functions; and (3) further define the functional role of T cell glycoproteins expressed on the majority of human T cells including T1, T3 and T11 antigens. This will involve functional studies to determine the importance of these molecules in T cell triggering, activation and recognition. In many of these studies we should emphasize that we plan to analyze not only freshly isolated populations of human T cells but also IL-2 dependent T cell clones and murine fibroblasts expressing human T cell glycoproteins after DNA mediated transfer of genes encoding these molecules. These studies will be essential to further the understanding of human diseases involving immunodeficiency and/or imbalances in the regulation of T cell function including AIDS, autoimmune states and neoplastic states.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI014969-10
Application #
3125950
Study Section
Immunological Sciences Study Section (IMS)
Project Start
1978-04-01
Project End
1989-03-31
Budget Start
1987-04-01
Budget End
1988-03-31
Support Year
10
Fiscal Year
1987
Total Cost
Indirect Cost
Name
Columbia University (N.Y.)
Department
Type
Schools of Medicine
DUNS #
064931884
City
New York
State
NY
Country
United States
Zip Code
10027
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Cleary, A M; Fortune, S M; Yellin, M J et al. (1995) Opposing roles of CD95 (Fas/APO-1) and CD40 in the death and rescue of human low density tonsillar B cells. J Immunol 155:3329-37
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Lederman, S; Yellin, M J; Cleary, A M et al. (1994) T-BAM/CD40-L on helper T lymphocytes augments lymphokine-induced B cell Ig isotype switch recombination and rescues B cells from programmed cell death. J Immunol 152:2163-71
Yellin, M J; Sippel, K; Inghirami, G et al. (1994) CD40 molecules induce down-modulation and endocytosis of T cell surface T cell-B cell activating molecule/CD40-L. Potential role in regulating helper effector function. J Immunol 152:598-608
Lederman, S; Yellin, M J; Covey, L R et al. (1993) Non-antigen signals for B-cell growth and differentiation to antibody secretion. Curr Opin Immunol 5:439-44
Lederman, S; Yellin, M J; Inghirami, G et al. (1992) Molecular interactions mediating T-B lymphocyte collaboration in human lymphoid follicles. Roles of T cell-B-cell-activating molecule (5c8 antigen) and CD40 in contact-dependent help. J Immunol 149:3817-26

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