Importance of minor histocompatibility antigen expression by nonhematopoietic tissues in a CD4+ T cell-mediated graft-versus-host disease model.
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.
Jones
Stephen C
SC
Kimmel Cancer Center, Jefferson Medical College, 233 South Tenth Street, Philadelphia, Pennsylvania 19107, USA.
Murphy
George F
GF
Friedman
Thea M
TM
Korngold
Robert
R
D000818:Animals; D000911:Antibodies, Monoclonal / Q000378:metabolism; D001853:Bone Marrow / Q000378:metabolism; D016026:Bone Marrow Transplantation; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism*; D005260:Female; D005434:Flow Cytometry; D006086:Graft vs Host Disease / Q000276:immunology* / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D015778:Minor Histocompatibility Antigens / Q000096:biosynthesis*; D013997:Time Factors
D000911:Antibodies, Monoclonal; D015778:Minor Histocompatibility Antigens