CD8 T cells specific for a donor-derived, self-restricted transplant antigen are nonpathogenic bystanders after vascularized heart transplantation in mice.
CD8 T cell cross-priming, an established mechanism of protective antiviral immunity, was originally discovered during studies involving minor transplantation Ags. It is unclear whether or how cross-primed CD8 T cells, reactive to donor-derived, but recipient class I MHC-restricted epitopes, could injure a fully MHC-disparate, vascularized transplant. To address this question we studied host class I MHC-restricted, male transplantation Ag-reactive T cell responses in female recipients of fully MHC-disparate, male heart transplants. Cross-priming to the immune-dominant determinant HYUtyp occurred at low frequency after heart transplantation. CD8 T cell preactivation through immunization with HYUtyp mixed in CFA did not alter the kinetics of acute rejection. Furthermore, neither HYUtyp immunization nor adoptive transfer of HYUtyp-specific TCR-transgenic T cells affected outcome in 1) a model of chronic rejection in the absence of immunosuppression or 2) a model of allograft acceptance induced by costimulatory blockade. The results support the contention that CD8 T cells reactive to host-restricted, but donor-derived, Ags are highly specific and are nonpathogenic bystanders during rejection of MHC-disparate cardiac allografts.
Valujskikh
Anna
A
Department of Immunology, Lerner Research Institute, Cleveland Clinic Foundation, OH 44195, USA.
Zhang
Qiwei
Q
Heeger
Peter S
PS
D000208:Acute Disease; D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002908:Chronic Disease; D003331:Coronary Vessels / Q000276:immunology*; D045142:Cross-Priming; D005260:Female; D006084:Graft Rejection / Q000276:immunology*; D006335:Heart Injuries; D016027:Heart Transplantation / Q000276:immunology* / Q000473:pathology; D015395:Histocompatibility Antigens Class I / Q000276:immunology*; D008297:Male; D051379:Mice; D018919:Neovascularization, Physiologic; D012867:Skin / Q000276:immunology; D016038:Skin Transplantation; D014019:Tissue Donors; D014184:Transplantation, Homologous
D015395:Histocompatibility Antigens Class I