Journal
TRANSPLANT IMMUNOLOGY
Volume 24, Issue 2, Pages 119-126Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.trim.2010.11.003
Keywords
DNT cell; Treg cells; Transplantation; Heart; Rapamycin
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Funding
- Heart and Stroke Foundation of Canada
- Canadian Institutes of Health (CIHR)
- University of Western Ontario, London, Ontario, Canada
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Regulatory T (Treg) cells play an important role in the regulation of immune responses but whether Treg will induce tolerance in transplant recipients in the clinic remains unknown. Our previous studies have shown that TCR alpha beta(+)CD3(+)CD4(-)CD8(-)NK1.1(-) (double negative, UN) T cells suppress T cell responses and prolong allograft survival in a single locus MHC-mismatched mouse model. In this study, we investigated the role of DNT cells in a more robust, fully MHC-mismatched BALB/c to C57BL/6 transplantation model, which may be more clinically relevant. Adoptive transfer of DNT cells in combination with short-term rapamycin treatment (days 1-9) induced long-term heart allograft survival (101 +/- 31 vs. 39 +/- 13 days rapamycin alone, p<0.01). Furthermore adoptive transfer DNT cells augmented CD4+Foxp3+ Treg cells accumulation in transplant recipients while depletion of CD4(+) Treg cells by anti-CD25 inhibited the effect of DNT cells on long-term graft survival (48 +/- 12 days vs. 101 +/- 31 days, p<0.001). In conclusion, DNT cells combined with short-term immunosuppression can prolong allograft survival, which may be through the accumulation of CD4(+)Foxp3(+) Treg cells in the recipient. Our result suggests that allograft tolerance may require the co-existence of different type Treg cell phenotypes which are affected by current immunosuppression. (C) 2010 Elsevier B.V. All rights reserved.
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