Our research is directed to revealing how cytolytic T lymphocytes are generated, regulated and terminated in vivo toward altered-self antigens. We induce CTLs by injecting H-2 compatible, minor locus (Mls) histo-incompatible cells along with tri-nitrophenylated self spleen cells. The former stimulate helper T cells to make soluble factors required by pre-CTLs that are activated by TNP-H-2K,D antigens. Mature CTLs, recoverable from popliteal lymph nodes draining injection sites are highly specific for the haptenated self antigens. We have studied down-regulation of this response using immunotolerance and other techniques. We have reported that a single suppressor T cell that prevents appearance of CTLs is inducible by two separate methods. One involves inducing tolerance to the same Mls antigen that is used to stimulate help. The other involves pre-exposing popliteal lymph nodes to syngeneic spleen cells before attempting sensitization for CTLs. The antigen responsible for eliciting the Ts in the latter case is unknown. Suppression by both Ts is directed to some aspect of help and each cell makes a soluble factor. Distinct from this is our finding that two hapten-induced Ts cells apparently act in tandem to prevent appearance of CTLs. The two Ts are initiated by widely different methods and are readily differentiable from each other. Neither cell, alone, will prevent CTL generation. Both Ts cells must be present during the afferent or inductive phase of sensitization to interrupt CTL maturation. We will characterize the Ts cells of both systems with respect to phenotype, binding specificity, soluble products, and mechanisms of action. We are concerned with whether each suppressor system affects precursors of CTLs or production of helper factors from T cells or macrophages. Acquisition of this information is important to our understanding of the manner in which CTLs are induced and regulated. Cell mediated lysis is a vital part of the body's immunological armamentarium since it is important in tissue graft and tumor rejection as well as perhaps in certain types of autoimmune diseases.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI017657-06
Application #
3127351
Study Section
Immunological Sciences Study Section (IMS)
Project Start
1981-09-01
Project End
1989-05-31
Budget Start
1988-06-01
Budget End
1989-05-31
Support Year
6
Fiscal Year
1988
Total Cost
Indirect Cost
Name
Cleveland Clinic Lerner
Department
Type
DUNS #
017730458
City
Cleveland
State
OH
Country
United States
Zip Code
44195
Matriano, J A; Battisto, J R (1991) Peripheral tolerance induced in lymph nodes by syngeneic spleen cells inhibits generation of CTLs to hapten-altered self antigens but not to alloantigens. Cell Immunol 136:16-28
Kuo, T S; Matriano, J; Ferguson, T A et al. (1989) Suppressor T cells induced by epidermally applied hapten are located in bone marrow. Reg Immunol 2:399-407
Chow, K P; Battisto, J R (1988) Down-regulation of cytotoxic T lymphocyte development by a minor stimulating locus-induced suppressor cascade that involves Lyt-1+ suppressor T cells, IA- macrophages, and their factors. J Immunol 140:1005-13
Battisto, J R; Gautam, S C; Chow, K N (1988) Down-regulation of cytotoxic T lymphocyte generation by two distinct suppressor-cell systems. Ann N Y Acad Sci 532:177-98
Battisto, J R; Dustoor, M M (1987) Allogeneic and autologous mixed lymphocyte reactions. Methods Enzymol 150:83-91
Emara, M; Battisto, J R (1987) The suppressor T cell induced by syngeneic splenic cell antigen down-regulates hapten-specific cytotoxic T cells by elaborating a factor inhibitory for IL2-dependent cell replication. Cell Immunol 105:220-34
Emara, M; Battisto, J R (1987) A syngeneic splenic cell antigen induces a suppressor T cell in lymph nodes that controls cytotoxic T-cell and primary antibody responses. Cell Immunol 105:205-19
Wong, H L; Battisto, J R (1985) Ongoing hapten-specific delayed-type hypersensitivity prevents generation of cytolytic T lymphocytes to the same hapten. Cell Immunol 94:205-14