Mechanisms of Regulation of Cell-Mediated Immunity

Abstract

Abstract We have investigated the induction, transfer, and suppression of delayed-type hypersensitivity (DTH) to the hapten azobenzenearsonate (ABA), using ABA-derivatized spleen cells in mice. It was found that ABA-derivatized syngeneic cells administered subcutaneously induced hapten-specific DTH responses detected by footpad swelling upon challenge with similarly ABA-modified syngeneic cells, but not with syngeneic cells modified with an irrelevant hapten. The footpad response was determined to be a manifestation of cell-mediated immunity (CMI) from the time course of the reactivity, the characteristic histology, and the results of adoptive transfer experiments. Negative selection experiments with anti-Thy 1.2 antiserum and complement demonstrated that the response was thymic dependent (T) and was transferable to naive recipients by immune T cells but not by immune sera. The induction and elicitation of the response required, minimally, identity at the I-A region of the H-2 major histocompatibility complex (MHC) between the immunizing hapten-modified cell and the recipient. Further studies revealed that syngeneic ABA-modified adherent cells were more capable of inducing ABA-specific DTH responses than similarly derivatized nonadherent cells. Studies dealing with the presentation of hapten with (BALB/c × A/J)F1 derivatized cells as immunogens indicated that F1 immune mice appeared to respond preferentially to BALB/c hapten cell surface conjugates rather than A/J cell surface as assessed by challenge of F1 immune mice with modified parental cells of either type. In adoptive transfer experiments it was found that immune T cells could transfer reactivity if, and only if, the immune T cells, the recipient, and the challenging modified cell were syngeneic or semisyngeneic. Allogeneic transfers were unsuccessful, even when the priming cells, the immune T cells, and challenge were syngeneic, but the recipient was not. The apparent failure of allogeneic transfer was not due to the presence of suppressor cells. Finally, we were able to elicit suppressor T cells by the i.v. administration of ABA-modified syngeneic cells. ABA-specific suppressor T cells limit the generation of DTH to ABA-modified cells, but do not decrease DTH to cells modified with an irrelevant hapten.