Microchimerism maintains deletion of the donor cell-specific CD8+ T cell repertoire

Publication

Microchimerism maintains deletion of the donor cell-specific CD8+ T cell repertoire

Journal Paper/Review - Jan 1, 2006

Bonilla Weldy V, Geuking Markus B, Aichele Peter, Ludewig Burkhard, Hengartner Hans, Zinkernagel Rolf M

Citation

Bonilla W, Geuking M, Aichele P, Ludewig B, Hengartner H, Zinkernagel R. Microchimerism maintains deletion of the donor cell-specific CD8+ T cell repertoire. The Journal of clinical investigation 2006; 116:156-62.

Type

Journal Paper/Review (English)

Journal

The Journal of clinical investigation 2006; 116

Publication Date

Jan 1, 2006

Issn Print

0021-9738

Pages

156-62

Brief description/objective

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.