Analysis of graft-versus-host disease (GVHD) and graft rejection using MHC class I-deficient mice

S. Shenoy, K. Desch, B. Duffy, P. Thorson, T. Mohanakumar

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5 Scopus citations


GVHD is a major complication in allogeneic bone marrow transplantation (BMT). MHC class I mismatching increases GVHD, but in MHC-matched BMT minor histocompatibility antigens (mH) presented by MHC class I result in significant GVHD. To examine the modification of GVHD in the absence of cell surface MHC class I molecules, β2-microglobulin-deficient mice (β2m-/-) were used as allogeneic BMT recipients in MHC- and mH-mismatched transplants. β2m-/- mice accepted MHC class I-expressing BM grafts and developed significant GVHD. MHC (H-2)-mismatched recipients developed acute lethal GVHD. In contrast, animals transplanted across mH barriers developed indolent chronic disease that was eventually fatal. Engrafted splenic T cells in all β2m-/- recipients were predominantly CD3+αβTCR+CD4+ cells (15-20% of all splenocytes). In contrast, CD8+ cells engrafted in very small numbers (1-5%) irrespective of the degree of MHC mismatching. T cells proliferated against recipient strain antigens and recognized recipient strain targets in cytolytic assays. Cytolysis was blocked by anti-MHC class II but not anti- CD8 or anti-MHC class I monoclonal antibodies (MoAbs). Cytolytic CD4+ T cells induced and maintained GVHD in mH-mismatched β2m-/mice, supporting endogenous mH presentation solely by MHC class II. Conversely, haematopoietic β2m-/- cells were unable to engraft in normal MHC-matched recipients, presumably due to natural killer (NK)-mediated rejection of class I-negative cells. Donor-derived lymphokine-activated killer cells (LAK) were unable to overcome graft rejection (GR) and support engraftment.

Original languageEnglish
Pages (from-to)188-195
Number of pages8
JournalClinical and Experimental Immunology
Issue number2
StatePublished - 1998


  • CD4 cells
  • GVHD
  • Graft rejection
  • MHC class II
  • βm-/- mice


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