Microchimerism maintains deletion of the donor cell-specific CD8+ T cell repertoire.
Rare cases of stable allograft acceptance after discontinuation of immunosuppression are often accompanied by macrochimerism (> 1% donor cells in blood) or microchimerism (< 1% donor cells in blood). Here, we have investigated whether persistence of donor cells is the cause or the consequence of long-lasting CTL unresponsiveness. We found that engraftment of splenocytes bearing a single foreign MHC class I-restricted epitope resulted in lifelong donor cell microchimerism and specific CTL unresponsiveness. This status was reversed in a strictly time- and thymus-dependent fashion when the engrafted cells were experimentally removed. The results presented herein show that microchimerism actively maintains CTL unresponsiveness toward a minor histocompatibility antigen by deleting the specific repertoire and thus excluding dominant, T cell extrinsic mechanisms of CTL unresponsiveness independent of systemically persisting donor cell antigen.
Bonilla
Weldy V
WV
Institute of Experimental Immunology, Department of Pathology, University Hospital Zurich, Zurich, Switzerland.
Geuking
Markus B
MB
Aichele
Peter
P
Ludewig
Burkhard
B
Hengartner
Hans
H
Zinkernagel
Rolf M
RM
D019264:Adoptive Transfer; D000818:Animals; D003433:Crosses, Genetic; D015395:Histocompatibility Antigens Class I / Q000276:immunology; D007519:Isoantigens / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D013934:Thymectomy; D018183:Transplantation Chimera; D014184:Transplantation, Homologous / Q000276:immunology*
D015395:Histocompatibility Antigens Class I; D007519:Isoantigens