Adoptive immunotherapy is suppressed in C57BL/6J AND B6.C‐H‐2bm12 mice following recognition of congenic class II MHC antigen determinants

Abstract

In previous reports, we have shown that adoptive transfer of tumor-sensitized T (immune) cells to tumor-bearing mice that have received a prior injection of cyclophosphamide (CY) results in the induction of permanent tumor regression in syngeneic strains. It has also been shown that adoptive immunotherapy results in an increased expression of class II MHC antigens (Ia) by macrophages at the tumor site and in the peritoneal cavity and is associated with expansion of CD4+ and CD8+ T cells at the site of tumor regression. In this report, we use the Ia mutant strain, B6.C-H-2bm12, and congenic C57BL/6J (B6) mice to determine the relative importance of Ia expression in regulating amplification of immune responses following adoptive immunotherapy and to test the hypothesis that recognition of congenic Ia determinants will result in the induction of suppressor mechanisms that down-regulate active immunity. The data indicated that the adoptive transfer of immune congenic T cells (B6 immune cells into CY-treated tumor-bearing bm12 mice and vice-versa) down-regulated active immunity, while the transfer of syngeneic immune cells resulted in permanent tumor regression. By using radiation-chimeric mice, it was shown that down-regulation was associated with incompatibility of the transferred immune T cells and bone-marrow-derived cells (putatively expressing the Ia haplotype of donor-derived macrophages) and the appearance of long-lived splenic suppressor cells. Suppression per se was shown to be induced in response to the Ia difference between the two strains and not in response to the MCA/76-9 sarcoma, which appears to be one of the few tumors that can induce active immunity in both the syngeneic and congenic strains without obvious subsequent down-regulation by suppression.