CD40Ig treatment results in allograft acceptance mediated by CD8+CD45RClow T cells, IFN-γ, and indoleamine 2,3-dioxygenase
J. Clin. Invest. Carole Guillonneau, et al. 117:1096 doi:10.1172/JCI28801 [
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Figure 1CD8
+ T cells mediate transfer of transplantation tolerance after CD40Ig treatment.
Cells from control rats that had rejected their grafts or from CD40Ig-treated recipients were injected i.v. the day of transplantation into LEW.1A recipients that received LEW.1W heart transplants (day 0) and that were sublethally irradiated (4.5 Gy, at day –1). (
A) Total splenocytes (50 × 10
6;
n = 6) or splenocytes depleted of T cells (
n = 2), CD4
+ cells (
n = 2), CD8
+ cells (
n = 4), or NK cells (
n = 2) were injected. (
B) Splenocytes (50 × 10
6;
n = 6), purified T cells (
n = 3), CD8
+ T cells (
n = 4), or CD4
+ T cells (
n = 2) were injected. Graft survival was assessed by abdominal palpation of cardiac beating. (
C) Grafts were either untreated (
n = 9; thick black line), treated with a control mAb (3G8) (
n = 6, gray line), transduced with Addl324 (5 × 10
10 IP;
n = 9; dotted line), transduced with AdCD40Ig (
n = 27, black line with open circles), or transduced with AdCD40Ig and injected with a depleting anti-CD8 mAb (OX8) (
n = 12; black line with open triangles) or an anti-MHC class I mAb (OX18) (
n = 3; black line with filled diamonds). A group of control animals received the control mAb (3G8) in addition to CD40Ig (
n = 6; black line with open diamonds). **
P < 0.01, ***
P < 0.0001 versus animals injected with AdCD40Ig or AdCD40Ig and 3G8.