Microchimerism maintains deletion of the donor cell–specific CD8+ T cell repertoire
Weldy V. Bonilla, … , Hans Hengartner, Rolf M. Zinkernagel
Weldy V. Bonilla, … , Hans Hengartner, Rolf M. Zinkernagel
Published January 4, 2006
Citation Information: J Clin Invest. 2006;116(1):156-162. https://doi.org/10.1172/JCI26565.
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Research Article Immunology

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

Abstract

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.

Authors

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

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