Regulatory T‐Cell Counter‐Regulation by Innate Immunity Is a Barrier to Transplantation Tolerance

Innate immune signals foster adaptive immunity through activation of antigen‐presenting cells. Recent in vitro evidence suggests that innate signaling may also contribute to immunity by countering the effects of regulatory T cells (T‐regs), counter‐regulation. We present in vivo evidence using a tra...

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Bibliographic Details
Published in:American journal of transplantation 2009-12, Vol.9 (12), p.2736-2744
Main Authors: Kim, J. I., Lee IV, M. K., Moore, D. J., Sonawane, S. B., Duff, P. E., O’Connor, M. R., Yeh, H., Lian, M. M., Deng, S., Caton, A. J., Markmann, J. F.
Format: Article
Language:English
Subjects:
Allograft
Animals
Antigen-Presenting Cells - physiology
Biological and medical sciences
Forkhead Transcription Factors - biosynthesis
Graft Rejection - immunology
Immune Tolerance - immunology
Immunity, Innate - immunology
inflammation
Inflammation - immunology
Medical sciences
Mice
Mice, Transgenic
Skin Transplantation - immunology
Surgery (general aspects). Transplantations, organ and tissue grafts. Graft diseases
T-Lymphocytes, Regulatory - immunology
tolerance
transplant
T‐reg
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Summary:Innate immune signals foster adaptive immunity through activation of antigen‐presenting cells. Recent in vitro evidence suggests that innate signaling may also contribute to immunity by countering the effects of regulatory T cells (T‐regs), counter‐regulation. We present in vivo evidence using a transgenic skin allograft model that the function of T‐regs is lost in the setting of acute skin transplantation but remains intact when grafts were transplanted 1 month prior to allow surgery‐induced inflammation to abate. Our findings identify T‐reg counter‐regulation as a naturally occurring process that accompanies transplantation and an important barrier to T‐reg–mediated tolerance. Our finding further highlights the central role of regulatory cell deactivation in the initiation of the immune response. Injury and inflammation resulting from the transplant procedure inactivate T‐reg‐mediated graft prolongation, in part, by downregulating Foxp3 levels in T‐regs.
ISSN:1600-6135
1600-6143
DOI:10.1111/j.1600-6143.2009.02847.x