TY - JOUR
T1 - Natural CD8+CD122+ T cells are more potent in suppression of allograft rejection than CD4+CD25+ regulatory T cells
AU - Dai, Z.
AU - Zhang, S.
AU - Xie, Q.
AU - Wu, S.
AU - Su, J.
AU - Li, S.
AU - Xu, Y.
AU - Li, X. C.
PY - 2014/1
Y1 - 2014/1
N2 - Despite extensive studies on CD4+CD25+ regulatory T cells (Tregs), their application in adoptive transfer therapies is still not optimal in immune-competent wild-type (WT) animal models. Therefore, it is compelling to search for more potent Tregs for potential clinical application. Mounting evidence has shown that naturally occurring CD8+CD122+ T cells are also Tregs. However, their suppression in allograft rejection, efficiency in suppression and underlying mechanisms remain unclear. Using a murine allotransplantation model, we reported here that CD8+CD122+ Tregs were actually more potent in suppression of allograft rejection and underwent more rapid homeostatic proliferation than their CD4+CD25+ counterparts. Moreover, they produced more IL-10 and were more potent in suppressing T cell proliferation in vitro. Deficiency in IL-10 in CD4+CD25+ and CD8+CD122+ Tregs resulted in their reduced but equal suppression in vivo and in vitro, suggesting that IL-10 is responsible for more effective suppression by CD8+CD122+ than CD4+CD25+ Tregs. Importantly, transfer of CD8+CD122+ Tregs together with the administration of recombinant IL-15 significantly prolonged allograft survival in WT mice. Thus, for the first time, we demonstrate that naturally arising CD8+CD122+ Tregs not only inhibit allograft rejection but also exert this suppression more potently than their CD4+CD25+ counterparts. This novel finding may have important implications for tolerance induction. In search of more efficient subsets of regulatory T cells, the authors find that naturally arising CD8+CD122+ T cells are more potent suppressors of allograft rejection than conventional CD4+CD25+ regulatory T cells. See editorial by Lerret and Luo on page 7.
AB - Despite extensive studies on CD4+CD25+ regulatory T cells (Tregs), their application in adoptive transfer therapies is still not optimal in immune-competent wild-type (WT) animal models. Therefore, it is compelling to search for more potent Tregs for potential clinical application. Mounting evidence has shown that naturally occurring CD8+CD122+ T cells are also Tregs. However, their suppression in allograft rejection, efficiency in suppression and underlying mechanisms remain unclear. Using a murine allotransplantation model, we reported here that CD8+CD122+ Tregs were actually more potent in suppression of allograft rejection and underwent more rapid homeostatic proliferation than their CD4+CD25+ counterparts. Moreover, they produced more IL-10 and were more potent in suppressing T cell proliferation in vitro. Deficiency in IL-10 in CD4+CD25+ and CD8+CD122+ Tregs resulted in their reduced but equal suppression in vivo and in vitro, suggesting that IL-10 is responsible for more effective suppression by CD8+CD122+ than CD4+CD25+ Tregs. Importantly, transfer of CD8+CD122+ Tregs together with the administration of recombinant IL-15 significantly prolonged allograft survival in WT mice. Thus, for the first time, we demonstrate that naturally arising CD8+CD122+ Tregs not only inhibit allograft rejection but also exert this suppression more potently than their CD4+CD25+ counterparts. This novel finding may have important implications for tolerance induction. In search of more efficient subsets of regulatory T cells, the authors find that naturally arising CD8+CD122+ T cells are more potent suppressors of allograft rejection than conventional CD4+CD25+ regulatory T cells. See editorial by Lerret and Luo on page 7.
KW - Allograft rejection
KW - T cell
KW - Treg
UR - http://www.scopus.com/inward/record.url?scp=84891030559&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84891030559&partnerID=8YFLogxK
U2 - 10.1111/ajt.12515
DO - 10.1111/ajt.12515
M3 - Article
C2 - 24219162
AN - SCOPUS:84891030559
VL - 14
SP - 39
EP - 48
JO - American Journal of Transplantation
JF - American Journal of Transplantation
SN - 1600-6135
IS - 1
ER -