The overall objective of the proposed research is to understand more about the mechanism(s) by which orally administered hapten regulates hapten-specific delayed-type hypersensitivity (DTH) and cell-mediated lympholysis (CML) toward hapten-altered self moieties. While significant progress has been made in ravelling underlying mechanisms of unresponsiveness induced by administering antigens parenterally, the mechanisms of tolerance induced via the gastrointestinal route are far from clear. We have previously reported a new protocol for generating cytolytic T lymphocytes (CTLs) toward hapten-altered self antigens in vivo without the need for eliminating naturally occurring cyclophosphamide sensitive suppressor T cell as reported by others. This has allowed us to make examinations of the development of both T cell mediated responses in vivo where the tolerance is induced by feeding. We have been able to report that both DTH and CML are suppressed when hapten is administered intragastrically. Yet whereas the unresponsiveness for DTH can be transferred readily with lymphoid cells, that for CML cannot. Thus, we wish to identify which of the suppressor T cell circuits that are triggered by parenterally administered antigens are also initiated by feeding the antigens. Upon identification we wish to know whether each is equally functional to suppress both responses. Besides suppressor cells we will determine whether hapten-specific antibodies, auto-anti-idiotypic antibodies and other nonspecific inhibitors that may regulate these T cell mediated immune responses are generated by feeding antigen. To resolve these questions we will use mice for both in vivo and in vitro experiments. The information gathered from this research proposal will permit identification of mechanism(s) by which DTH and CML responses are initiated, regulated and terminated by orally administered hapten. This knowledge will further improve our understanding of major clinical conditions such as environmentally induced allergic contact hypersensitivity, autoimmunity as well as graft and tumor rejection.
| Gautam, S C; Battisto, J R (1989) Feeding trinitrochlorobenzene inhibits development of hapten-specific cytotoxic T lymphocytes by interfering with helper T-cell function. Reg Immunol 2:33-41 |
| Gautam, S C; Beckman, K; Battisto, J R (1986) Natural cytotoxic T cells (NCTC) that differ from natural killer (NK) and natural cytotoxic (NC) cells are present in Peyer's patches of mice. Cell Immunol 101:463-75 |
