Alloantigen presentation to the anterior chamber of the eye subverts specific in vitro cell-mediated immune responses

Aberrant cell-mediated immune responses are produced when minor histocompatibility antigens expressed on tumor cells are placed in the anterior chamber of the mouse eye. Mice bearing intraocular histoincompatible tumors fail to develop alloimmunity as expressed by their failure to reject orthotopic skin grafts syngeneic with the tumor cells. The cellular basis of anterior chamber-associated immune deviation (ACAID) was examined in vitro by studying lymphoid cells from BALB/c mice that had received intracameral inoculations of P815 tumor cells. It was found that both proliferative and cytotoxic T cell responses to DBA/2 alloantigens were either low or absent. Splenectomy prior to intracameral inoculation of P815 cells produced the opposite effect, i.e., lymphoid cells from these animals performed in in vitro assays as though they were specifically primed to the DBA/2 alloantigens. In an effort to identify an active process of suppression as the possible basis for ACAID, mixing experiments were conducted in which the alloreactivities of normal lymphoid cells were subjected to putative regulator cells from animals with ACAID. No evidence of suppression of the response of animal cells to DBA/2 alloantigens was discerned. Thus, the aberrant cell-mediated responses of lymphoid cells from BALB/c mice bearing intraocular P815 tumors appear to be consistent with the hypothesis that clonal deletion among mature immunocompetent cells is responsible for the ACAID phenomenon.