CD25+CD4+ regulatory T cells develop in mice not only during spontaneous acceptance of liver allografts but also after acute allograft rejection.
BACKGROUND
Liver grafts transplanted across a major histocompatibility barrier are accepted spontaneously and induce donor specific tolerance in some species. Here, we investigated whether liver allograft acceptance is characterized by, and depends upon, the presence of donor reactive CD25CD4 regulatory T cells.


METHODS
CD25 and CD25CD4 T cells, isolated from CBA. Ca (H2) recipients of C57BL/10 (B10; H2) liver and heart allografts 10 days after transplantation, were transferred into CBA. Rag1 mice to investigate their influence on skin allograft rejection mediated by CD45RBCD4 effector T Cells.


RESULTS
Fully allogeneic B10 liver allografts were spontaneously accepted by naive CBA.Ca recipient mice, whereas B10 cardiac allografts were acutely rejected (mean survival time=7 days). Strikingly, however, CD25CD4 T cells isolated from both liver and cardiac allograft recipients were able to prevent skin allograft rejection in this adoptive transfer model. Interestingly, CD25CD4 T cells isolated from liver graft recipients also showed suppressive potency upon adoptive transfer. Furthermore, depletion of CD25CD4 T cells in primary liver allograft recipients did not prevent the acceptance of a secondary donor-specific skin graft.


CONCLUSIONS
Our data provide evidence that the presence of CD25CD4 regulatory T cells is not a unique feature of allograft acceptance and is more likely the result of sustained exposure to donor alloantigens in vivo.
Steger
Ulrich
U
Nuffield Department of Surgery, University of Oxford, John Radcliffe Hospital, Oxford, United Kingdom. ulrich.steger@mail.uni-wuerzburg.de
Kingsley
Cherry I
CI
Karim
Mahzuz
M
Bushell
Andrew R
AR
Wood
Kathryn J
KJ
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D015704:CD4 Antigens / Q000032:analysis; D006084:Graft Rejection / Q000276:immunology; D006085:Graft Survival / Q000276:immunology; D016027:Heart Transplantation; D053645:Interleukin-2 Receptor alpha Subunit / Q000032:analysis / Q000037:antagonists & inhibitors; D016031:Liver Transplantation / Q000276:immunology*; D008213:Lymphocyte Activation; D008212:Lymphocyte Depletion; D051379:Mice; D008815:Mice, Inbred Strains; D016038:Skin Transplantation / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects / Q000276:immunology*; D023001:Transplantation Tolerance
D000911:Antibodies, Monoclonal; D015704:CD4 Antigens; D053645:Interleukin-2 Receptor alpha Subunit