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  • Title: Endogenous superantigens in allogeneic bone marrow transplant recipients rapidly and selectively expand donor T cells which can produce IFN-gamma.
    Author: Jones MS, Riley R, Hamilton BL, Paupe J, Perez D, Levy RB.
    Journal: Bone Marrow Transplant; 1994 Nov; 14(5):725-35. PubMed ID: 7889005.
    Abstract:
    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 V beta TcR expression and IFN-gamma 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 V beta 3. A similar rapid and selective expansion of V beta 3+ TcR bearing donor T cells was detected in two other H-2 matched superantigen disparate donor-recipient BMT combinations. An increased percentage of V beta 3+ 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-gamma specific mRNA was readily detected in the spleens of B10.D2-->BALB/cBMT recipients containing large numbers of V beta 3+ T cells. Moreover, V beta 3+ donor T cells from these recipients contained IFN-gamma mRNA. Specific stimulation in vitro with immobilized anti-TcR moAbs demonstrated that V beta 3+ T cells secreted a large amount of the total IFN-gamma 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.
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