Cross-primed CD8(+) T cells mediate graft rejection via a distinct effector pathway.
To prevent bystander destruction of healthy host tissues, cytotoxic CD8(+) T lymphocytes are fitted with specific receptors that direct their destructive forces specifically against chosen targets. We show here, however, that anti-H-Y monospecific, H-2(b-restricted MataHari CD8(+) T cells reject H-2(k) male skin grafts, with which they cannot directly interact. Such rejection is interferon-gamma-dependent and only occurs if the recipient endothelium expresses H-2(b). The findings suggest an alternate indirect effector pathway that requires processing and presentation of the donor H-Y antigen by recipient endothelium and have implications for both transplantation and autoimmune disease.
Valujskikh
Anna
A
Department of Immunology, Lerner Research Institute, The Cleveland Clinic Foundation, Cleveland, OH 44195, USA.
Lantz
Olivier
O
Celli
Susanna
S
Matzinger
Polly
P
Heeger
Peter S
PS
D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D004730:Endothelium, Vascular / Q000166:cytology / Q000502:physiology; D005260:Female; D006084:Graft Rejection / Q000276:immunology*; D006183:H-2 Antigens / Q000502:physiology; D016027:Heart Transplantation / Q000276:immunology; D007371:Interferon-gamma / Q000502:physiology; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D016038:Skin Transplantation / Q000276:immunology; D014184:Transplantation, Homologous
D006183:H-2 Antigens; D007371:Interferon-gamma