The proposed studies are directed at the definition of critical surface molecules, factors, and cell interactions involved in thymocyte maturation. The intention is to investigate in detail the involvement of specific thymocyte surface molecules in human thymocyte activation and differentiation. For this purpose an in vitro thymocyte culture system, which has been developed and characterized by the applicant, will be used. Monoclonal antibodies to T cell antigens will be used to isolate relevant thymic subpopulations as well as to probe the role of the selected thymocyte surface antigens in the mediation or regulation of discrete stages of thymocyte maturation. Monoclonal antibodies to T cell surface antigens, MHC antigens, and specific lymphokines will be utilized for a detailed investigation of interactions between isolated subpopulations of immature thymocytes and non-T cells. These studies will take advantage of the availability of a large panel of monoclonal antibodies and the development of fluorescence flow cytometric techniques (including two color fluorescence) for the isolation of thymic subpopulations and the analysis of thymic surface antigen expression. These studies will take advantage of the availability of recombinant or purified lymphokines which may be critical in thymocyte development and growth. In addition to defining critical thymocyte surface molecules and factors, it is hoped that these studies may lead to an understanding of regulatory events and MHC restrictions which occur during thymic ontogeny. The information gained may contribute greatly to our understanding of normal human T cell differentiation and abnormal T cell differentiation which occurs in various T cell malignancies, autoimmune and immunodeficiency diseases.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Unknown (R23)
Project #
5R23AI023392-02
Application #
3445822
Study Section
Immunobiology Study Section (IMB)
Project Start
1986-04-01
Project End
1989-03-31
Budget Start
1987-04-01
Budget End
1988-03-31
Support Year
2
Fiscal Year
1987
Total Cost
Indirect Cost
Name
Dana-Farber Cancer Institute
Department
Type
DUNS #
149617367
City
Boston
State
MA
Country
United States
Zip Code
02115
Blue, M L; Levine, H; Daley, J F et al. (1989) Expression of CD1 and class I MHC antigens by human thymocytes. J Immunol 142:2714-20
Blue, M L; Daley, J F; Levine, H et al. (1989) Regulation of CD4 and CD8 surface expression on human thymocyte subpopulations by triggering through CD2 and the CD3-T cell receptor. J Immunol 142:374-80
Blue, M L; Craig, K A; Anderson, P et al. (1988) Evidence for specific association between class I major histocompatibility antigens and the CD8 molecules of human suppressor/cytotoxic cells. Cell 54:413-21
Anderson, P; Blue, M L; Schlossman, S F (1988) Comodulation of CD3 and CD4. Evidence for a specific association between CD4 and approximately 5% of the CD3:T cell receptor complexes on helper T lymphocytes. J Immunol 140:1732-7
Rudd, C E; Trevillyan, J M; Dasgupta, J D et al. (1988) The CD4 receptor is complexed in detergent lysates to a protein-tyrosine kinase (pp58) from human T lymphocytes. Proc Natl Acad Sci U S A 85:5190-4
Blue, M L; Hafler, D A; Daley, J F et al. (1988) Regulation of T cell clone function via CD4 and CD8 molecules. Anti-CD4 can mediate two distinct inhibitory activities. J Immunol 140:376-83
Anderson, P; Blue, M L; Morimoto, C et al. (1988) Crosslinking CD3 with CD2 using sepharose-immobilized antibodies enhances T lymphocyte proliferation. Cell Immunol 115:246-56
Anderson, P; Blue, M L; Morimoto, C et al. (1987) Cross-linking of T3 (CD3) with T4 (CD4) enhances the proliferation of resting T lymphocytes. J Immunol 139:678-82
Blue, M L; Daley, J F; Levine, H et al. (1987) Identification and isolation of a T4+T8+ cell with high T3 expression in human thymus: a possible late intermediate in thymocyte differentiation. J Immunol 139:1065-9
Blue, M L; Levine, H; Daley, J F et al. (1987) Development of natural killer cells in human thymocyte culture: regulation by accessory cells. Eur J Immunol 17:669-73

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