Endogenous superantigens in allogeneic bone marrow transplant recipients rapidly and selectively expand donor T cells which can produce IFN-γ

Despite the existence of many non-MHC disparities between MHC matched but non-MHC mismatched donors and recipients, graft-versus-host disease (GVHD) is not clinically apparent following a significant number of allogeneic bone marrow transplants (BMT) in experimental animals. The present studies examined Vβ TcR expression and IFN-γ production by donor T cells in a BMT model involving an MHC matched, allogeneic donor-recipient combination which included a unidirectional superantigen disparity (Mls). B10.D2→BALB/c, but not BALB/c→B10.D2 recipients develop GVHD and mortality ensues 8-12 weeks post-transplant. During the first 2 weeks post-transplant of B10.D2→BALB/c, approximately 50% of all Thy1.2⁺ spleen and lymph node cells were found to express T cell receptors utilizing Vβ3. A similar rapid and selective expansion of Vβ3⁺ TcR bearing donor T cells was detected in two other H-2 matched superantigen disparate donor-recipient BMT combinations. An increased percentage of Vβ3⁺ T cells was noted among both the CD4⁺ and CD8⁺ populations. Thus, in these donor/recipient combinations, all TcR families were not equally expanded early following transplant. At 4-10 days post-transplant, IFN-γ specific mRNA was readily detected in the spleens of B10.D2→BALB/cBMT recipients containing large numbers of Vβ3⁺ T cells. Moreover, Vβ3⁺ donor T cells from these recipients contained IFN-γ mRNA. Specific stimulation in vitro with immobilized anti-TcR moAbs demonstrated that Vβ3⁺ T cells secreted a large amount of the total IFN-γ levels detected. The ability of endogenous superantigens to activate large numbers of T cells which can produce cytokines after BMT indicates that when present, such antigenic differences may contribute to events occurring during initial graft-versus-host reactions. Such antigens could therefore participate in the events influencing whether GVHD develops following BMT between certain donors and recipients.