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Importance of minor histocompatibility antigen expression by nonhematopoietic tissues in a CD4+ T cell–mediated graft-versus-host disease model
Stephen C. Jones, … , Thea M. Friedman, Robert Korngold
Stephen C. Jones, … , Thea M. Friedman, Robert Korngold
Published December 15, 2003
Citation Information: J Clin Invest. 2003;112(12):1880-1886. https://doi.org/10.1172/JCI19427.
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Article Transplantation

Importance of minor histocompatibility antigen expression by nonhematopoietic tissues in a CD4+ T cell–mediated graft-versus-host disease model

Abstract

Minor histocompatibility antigens with expression restricted to the recipient hematopoietic compartment represent prospective immunological targets for graft-versus-leukemia therapy. It remains unclear, however, whether donor T cell recognition of these hematopoietically derived minor histocompatibility antigens will induce significant graft-versus-host disease (GVHD). Using established bone marrow irradiation chimeras across the multiple minor histocompatibility antigen–disparate, C57BL/6→BALB.B combination, we studied the occurrence of lethal GVHD mediated by CD4+ T cells in recipient mice expressing only hematopoietically derived alloantigens. Even substantial dosages of donor C57BL/6 CD4+ T cells were unable to elicit lethal GVHD when transplanted into [BALB.B→C57BL/6] chimeras. Instead, chimeric mice displayed transient cachexia with reduced target-tissue injury over time, reflecting an early, limited, graft-versus-host response. On the other hand, the importance of minor histocompatibility antigens derived from nonhematopoietic tissues was demonstrated by the finding that [C57BL/6→BALB.B] chimeric mice succumbed to C57BL/6 CD4+ T cell–mediated GVHD. These data suggest that severe acute CD4+ T cell–mediated GVHD across this minor histocompatibility antigen barrier depends on the expression of nonhematopoietically rather than hematopoietically derived alloantigens for maximal target-tissue infiltration and injury.

Authors

Stephen C. Jones, George F. Murphy, Thea M. Friedman, Robert Korngold

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