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

M. S. Jones, Richard L Riley, B. L. Hamilton, J. Paupe, D. Perez, Robert B Levy

Research output: Contribution to journalArticle

13 Citations (Scopus)

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 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.

Original languageEnglish
Pages (from-to)725-735
Number of pages11
JournalBone Marrow Transplantation
Volume14
Issue number5
StatePublished - Dec 1 1994

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Superantigens
Bone Marrow
Tissue Donors
T-Lymphocytes
Transplants
Graft vs Host Disease
Spleen
Transplant Recipients
Messenger RNA
Aptitude
T-Cell Antigen Receptor
Lymph Nodes
Cytokines
Antigens

ASJC Scopus subject areas

  • Hematology
  • Transplantation

Cite this

Endogenous superantigens in allogeneic bone marrow transplant recipients rapidly and selectively expand donor T cells which can produce IFN-γ. / Jones, M. S.; Riley, Richard L; Hamilton, B. L.; Paupe, J.; Perez, D.; Levy, Robert B.

In: Bone Marrow Transplantation, Vol. 14, No. 5, 01.12.1994, p. 725-735.

Research output: Contribution to journalArticle

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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 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.",
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