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 disease following autologous bone marrow transplantation in an attempt to destroy residual leukemia cells and reduce relapse. To analyze the antitumor potential of murine syngeneic graft-versus-host disease (SGVHD), C3H/HeN mice were lethally irradiated, reconstituted with T cell-depleted syngeneic bone marrow (ATBM) and treated with CsA for 21 days. Graft-versus-leukemia activity 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 graded 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 injected 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 75% of these mice died following injection of 500 38C13 tumor cells (MST = 34 days). Long-term survivors were not resistant to tumor challenge suggesting that tumor-specific immunity did not develop. Finally, class II 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 exist in SGVHD mice.
Bryson
J S
JS
Department of Internal Medicine, Chandler Medical Center, University of Kentucky, Lexington 40536-0093, USA.
Jennings
C D
CD
Lowery
D M
DM
Carlson
S L
SL
Pflugh
D L
DL
Caywood
B E
BE
Kaplan
A M
AM
D000818:Animals; D016026:Bone Marrow Transplantation; D006086:Graft vs Host Disease; D020350:Graft vs Tumor Effect; D000949:Histocompatibility Antigens Class II / Q000276:immunology; D016393:Lymphoma, B-Cell / Q000276:immunology* / Q000473:pathology* / Q000628:therapy; D051379:Mice; D008809:Mice, Inbred C3H; D014182:Transplantation, Autologous; D014185:Transplantation, Isogeneic
D000949:Histocompatibility Antigens Class II