Abstract

The overall aims of the present proposal are directed at the isolation and characterization of unique and still poorly characterized subpopulations of human T lymphocytes with the view that such cells may be centrally involved in the circuits which both up and down regulate the human immune response. The intention is to take advantage of major recent developments in methods for the generation of antibodies to cell surface antigens, for the isolation of purified subpopulations of cells, for the cloning of distinct populations of cells, and lastly for newer methods for the functional analysis of these populations of cells. In the present studies, we plan to undertake a detailed analysis of the phenotypic and functional properties of unique subpopulations of human T lymphocytes. In particular, we plan to develop monoclonal antibody probes to cell surface molecules which can divide the human inducer and suppressor populations into distinct subsets. To accomplish this, we plan to develop immunization and screening strategies which utilize primate lymphocyte populations, subsets of human peripheral T cells and cloned populations of functionally unique populations of human T cell lines. Once these antibodies are identified, we will separate both the inducer and suppressor populations into phenotypically unique subsets and investigate each for their regulatory effects on other human T, B and myeloid cells. The antibodies defined above will be utilized to characterize biochemically the cell surface structures they define. Moreover, attempts will be made to elucidate the function of the structures characterized. These antibodies will be useful in dissecting and characterizing patients with autoimmune and immunodeficiency diseases where the immunoregulatory circuit is clearly abnormal. Lastly, we will identify minor populations of T lymphocytes present both in normal peripheral blood and which can be cultured and determine whether these minor populations have distinct and unique functional programs.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI012069-15
Application #
3125103
Study Section
Allergy and Immunology Study Section (ALY)
Project Start
1978-10-01
Project End
1989-11-30
Budget Start
1987-12-01
Budget End
1989-11-30
Support Year
15
Fiscal Year
1988
Total Cost
Indirect Cost

  Institution

Name
Dana-Farber Cancer Institute
Department
Type
DUNS #
149617367
City
Boston
State
MA
Country
United States
Zip Code
02115

  Publications

Tang, Wen; Duke-Cohan, Jonathan S (2002) Human secreted attractin disrupts neurite formation in differentiating cortical neural cells in vitro. J Neuropathol Exp Neurol 61:767-77
Gensler, T J; Hottelet, M; Zhang, C et al. (2001) Monoclonal antibodies derived from BALB/c mice immunized with apoptotic Jurkat T cells recognize known autoantigens. J Autoimmun 16:59-69
Ma, F; Zhang, C; Prasad, K V et al. (2001) Molecular cloning of Porimin, a novel cell surface receptor mediating oncotic cell death. Proc Natl Acad Sci U S A 98:9778-83
Tang, W; Gunn, T M; McLaughlin, D F et al. (2000) Secreted and membrane attractin result from alternative splicing of the human ATRN gene. Proc Natl Acad Sci U S A 97:6025-30
Ikushima, H; Munakata, Y; Ishii, T et al. (2000) Internalization of CD26 by mannose 6-phosphate/insulin-like growth factor II receptor contributes to T cell activation. Proc Natl Acad Sci U S A 97:8439-44
Iwata, S; Yamaguchi, N; Munakata, Y et al. (1999) CD26/dipeptidyl peptidase IV differentially regulates the chemotaxis of T cells and monocytes toward RANTES: possible mechanism for the switch from innate to acquired immune response. Int Immunol 11:417-26
Wu, M X; Ao, Z; Prasad, K V et al. (1998) IEX-1L, an apoptosis inhibitor involved in NF-kappaB-mediated cell survival. Science 281:998-1001
Zhang, C; Xu, Y; Gu, J et al. (1998) A cell surface receptor defined by a mAb mediates a unique type of cell death similar to oncosis. Proc Natl Acad Sci U S A 95:6290-5
Duke-Cohan, J S; Gu, J; McLaughlin, D F et al. (1998) Attractin (DPPT-L), a member of the CUB family of cell adhesion and guidance proteins, is secreted by activated human T lymphocytes and modulates immune cell interactions. Proc Natl Acad Sci U S A 95:11336-41
Stuhler, G; Schlossman, S F (1997) Antigen organization regulates cluster formation and induction of cytotoxic T lymphocytes by helper T cell subsets. Proc Natl Acad Sci U S A 94:622-7

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