ENDOGENOUS SUPERANTIGENS IN ALLOGENEIC BONE-MARROW TRANSPLANT RECIPIENTS RAPIDLY AND SELECTIVELY EXPAND DONOR T-CELLS WHICH CAN PRODUCE IFN-GAMMA

Despite the existence of many non-MHC disparities between MHC matched but non-MHC mismatched donors and recipients, graft-versus-host diseas e (GVHD) is not clinically apparent following a significant number of allogeneic bone marrow transplants (BMT) in experimental animals. The present studies examined V beta TcR expression and IFN-gamma productio n by donor T cells in a BMT model involving an MHC matched, allogeneic donor-recipient combination which included unidirectional superantige n disparity (Mis), B10.D2 --> BALB/c, but not BALB/c --> B10.D2 recipi ents develop GVHD and mortality ensues 8-12 weeks post-transplant. Dur ing the first 2 weeks post-transplant of B10.D2 --> BALB/c, approximat ely 50% of all Thy1.2(+) spleen and lymph node cells were found to exp ress T cell receptors utilizing V beta 3, A similar rapid and selectiv e expansion of V beta 3(+) TcR bearing donor T cells was detected in t wo other H-2 matched superantigen disparate donor-recipient BMT combin ations. An increased percentage of V beta 3(+) T cells was noted among both the CD4(+) and CD8(+) populations. Thus, in these donor/recipien t combinations, all TcR families were not equally expanded early follo wing transplant. At 4-10 days post-transplant, IFN-gamma specific mRNA was readily detected in the spleens of B10.D2 --> BALB/cBMT recipient s containing large numbers of V beta 3(+) T cells, Moreover, V beta 3( +) donor T cells from these recipients contained IFN-gamma mRNA. Speci fic stimulation in vitro with immobilized anti-TcR moAbs demonstrated that V beta 3(+) T cells secreted a large amount of the total IFN-gamm a levels detected. The ability of endogenous superantigens to activate large numbers of T cells which can produce cytokines after BMT indica tes that when present, such antigenic differences may contribute to ev ents occurring during initial graft-versus-host reactions. Such antige ns could therefore participate in the events influencing whether GVHD develops following BMT between certain donors and recipients.