Rejection of an MHC class II negative tumor following induction of murine syngeneic graft-versus-host disease

Cyclosporin A (CsA) has been used clinically to induce graft-versus-host di sease following autologous bone marrow transplantation in an attempt to des troy residual leukemia cells and reduce relapse. To analyze the antitumor p otential of murine syngeneic graft-versus-host disease (SGVHD), C3H/HeN mic e were lethally irradiated, reconstituted with T cell-depleted syngeneic bo ne marrow (ATBM) and treated with CsA for 21 days. Graft-versus-leukemia ac tivity was assessed by challenging groups of olive oil-treated control ATBM (OO-ATBM) and CsA-treated (CsA-ATBM) mice 1 week after CsA therapy with gr aded doses of the syngeneic 38C13 B cell lymphoma. Following CsA treatment, up to 70% of CsA-ATBM developed SGVHD and more than 70% of the animals inj ected with 500 38C13 cells exhibited long-term survival (MST >80 days). In contrast, none of the OO-ATBM control mice developed SGVHD, and more than 7 5% of these mice died following injection of 500 38C13 tumor cells (MST = 3 4 days). Long-term survivors were not resistant to tumor challenge suggesti ng that tumor-specific immunity did not develop. Finally, class IT negative 38C13 cells cultured in IL-4 or IL-10 were not inducible for MHC class II molecules, demonstrating that class II-independent antitumor mechanisms exi st in SGVHD mice.