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 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.
Kim
J I
JI
Division of Surgery, Department of Transplantation, Massachusetts General Hospital, Boston, MA, USA.
Lee
M K
MK
Moore
D J
DJ
Sonawane
S B
SB
Duff
P E
PE
O'Connor
M R
MR
Yeh
H
H
Lian
M M
MM
Deng
S
S
Caton
A J
AJ
Markmann
J F
JF
D000818:Animals; D000938:Antigen-Presenting Cells / Q000502:physiology; D051858:Forkhead Transcription Factors / Q000096:biosynthesis; D006084:Graft Rejection / Q000276:immunology; D007108:Immune Tolerance / Q000276:immunology*; D007113:Immunity, Innate / Q000276:immunology*; D007249:Inflammation / Q000276:immunology; D051379:Mice; D008822:Mice, Transgenic; D016038:Skin Transplantation / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*
D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse