Type I interferons are not critical for skin allograft rejection or the generation of donor-specific CD8+ memory T cells.
Type I interferons (IFN-I) link innate to adaptive immunity in microbial infection, autoimmune disease and tumor immunity. It is not known whether IFN-I have an equally central role in alloimmunity. Here we tested this possibility by studying skin allograft survival and donor-specific CD8+ T-cell responses in mice that lack the IFN-I receptor (IFN-IR-/-). We found that IFN-IR-/- mice reject fully allogeneic wild-type skin grafts at the same rate as wild-type recipients. Similarly, allograft rejection was not delayed if IFN-IR-/- male skin was transplanted to syngeneic IFN-IR-/- female mice. Quantitation of the male (H-Y)-specific CD8+ T-cell response in these mice revealed normal generation of donor-specific CD8+ effector T cells but fourfold reduction in CD8+ memory T cells. Memory CD8+ T cells generated in the absence of IFN-IR had normal phenotype and recall function, assessed by ex vivo cytokine production and the ability of IFN-IR-/- mice to mount second set rejection. Finally, these memory T cells were maintained at a constant number despite their inability to respond to IFN-1. Our findings indicate that IFN-I cytokines are not critical for acute allograft rejection or for the expansion and differentiation of donor-specific CD8+ T cells into long-lived, functional memory T cells.
Oberbarnscheidt
M H
MH
Department of Surgery, Starzl Transplantation Institute, University of Pittsburgh, Pittsburgh, PA, USA.
Obhrai
J S
JS
Williams
A L
AL
Rothstein
D M
DM
Shlomchik
W D
WD
Chalasani
G
G
Lakkis
F G
FG
D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D005260:Female; D006084:Graft Rejection / Q000209:etiology / Q000276:immunology*; D007156:Immunologic Memory; D007370:Interferon Type I / Q000276:immunology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D017471:Receptors, Interferon / Q000172:deficiency / Q000235:genetics / Q000276:immunology; D016038:Skin Transplantation / Q000276:immunology*; D014184:Transplantation, Homologous
D007370:Interferon Type I; D017471:Receptors, Interferon