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2017 ; 8
(15
): 24187-24195
Nephropedia Template TP
gab.com Text
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English Wikipedia
Suppression of allograft rejection by CD8+CD122+PD-1+ Tregs is dictated by their
Fas ligand-initiated killing of effector T cells versus Fas-mediated own
apoptosis
#MMPMID28445940
Liu H
; Wang Y
; Zeng Q
; Zeng YQ
; Liang CL
; Qiu F
; Nie H
; Dai Z
Oncotarget
2017[Apr]; 8
(15
): 24187-24195
PMID28445940
show ga
Mounting evidence has shown that naturally occurring CD8+CD122+ T cells are
regulatory T cells (Tregs) that suppress both autoimmunity and alloimmunity. We
have previously shown that CD8+CD122+PD-1+ Tregs not only suppress allograft
rejection, but also are more potent in suppression than conventional CD4+CD25+
Tregs. However, the mechanisms underlying their suppression of alloimmunity are
not well understood. In an adoptive T-cell transfer model of mice lacking
lymphocytes, we found that suppression of skin allograft rejection by
CD8+CD122+PD-1+ Tregs was mostly dependent on their expression of Fas ligand as
either lacking Fas ligand or blocking it with antibodies largely abolished their
suppression of allograft rejection mediated by transferred T cells. Their
suppression was also mostly reversed when effector T cells lacked Fas receptor.
Indeed, these FasL+ Tregs induced T cell apoptosis in vitro in a
Fas/FasL-dependent manner. However, their suppression of T cell proliferation in
vitro was dependent on IL-10, but not FasL expression. Furthermore, adoptive
transfer of CD8+CD122+PD-1+ Tregs significantly extended allograft survival even
in wild-type mice if Tregs lacked Fas receptor or if recipients received
recombinant IL-15, as these two measures synergistically expanded
adoptively-transferred Tregs in recipients. Thus, this study may have important
implications for Treg therapies in clinical transplantation.