Open AccessRegulatory T cell expressed MyD88 is critical for prolongation of allograft survival
Author(s) -
Borges Christopher M.,
Reichenbach Dawn K.,
Kim Beom Seok,
Misra Aditya,
Blazar Bruce R.,
Turka Laurence A.
Publication year - 2016
Publication title -
transplant international
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.998
H-Index - 82
eISSN - 1432-2277
pISSN - 0934-0874
DOI - 10.1111/tri.12788
Subject(s) - medicine , effector , immunology , regulatory t cell , transplantation , t cell , cd154 , cell , graft versus host disease , homing (biology) , cancer research , in vitro , immune system , biology , cytotoxic t cell , il 2 receptor , ecology , biochemistry , genetics , cd40
Summary MyD88 signaling directly promotes T‐cell survival and is required for optimal T‐cell responses to pathogens. To examine the role of T‐cell‐intrinsic MyD88 signals in transplantation, we studied mice with targeted T‐cell‐specific MyD88 deletion. Contrary to expectations, we found that these mice were relatively resistant to prolongation of graft survival with anti‐ CD 154 plus rapamycin in a class II ‐mismatched system. To specifically examine the role of MyD88 in Tregs, we created a Treg‐specific MyD88‐deficient mouse. Transplant studies in these animals replicated the findings observed with a global T‐cell MyD88 knockout. Surprisingly, given the role of MyD88 in conventional T‐cell survival, we found no defect in the survival of MyD88‐deficient Tregs in vitro or in the transplant recipients and also observed intact cell homing and expression of Treg effector molecules. MyD88‐deficient Tregs also fail to protect allogeneic bone marrow transplant recipients from chronic graft‐versus‐host disease, confirming the observations of defective regulation seen in a solid organ transplant system. Together, our data define MyD88 as having a divergent requirement for cell survival in non‐Tregs and Tregs, and a yet‐to‐be defined survival‐independent requirement for Treg function during the response to alloantigen.