Interferon- and interleukin-4 reciprocally regulate CD8 expression in CD8 T cells

The CD8 co-receptor can modulate CD8 T cell function through its contributions to T cell receptor (TCR) binding and signaling. Here we show that IFNand IL-4 exert opposing effects on the expression of CD8 mRNA and surface CD8 protein during CD8 T cell activation. IL-4 caused down-regulation of surface CD8 on ovalbumin (OVA)257–264-specific TCR-transgenic OT-I CD8 T cells activated with OVA257–264-coated antigen presenting cells or polyclonal stimuli, and on wild type CD8 T cells activated with polyclonal stimuli. This effect was enhanced in each case when the cells lacked a functional IFNor IFNR gene. When WT or IFN-deficient OT-I CD8 T cells were analyzed 9 days after co-injection with control or IL-4-expressing OVA tumor cells into RAG-2 / c / mice, CD8 levels were highest on WT donor cells from mice that received the control tumor and lowest on IFN-deficient donor cells from mice that received the IL-4-expressing tumor. The latter CD8low cells displayed markedly impaired binding of OVA257–264/MHC tetramers and peptide/MHC-dependent degranulation. The data reveal an unexpected role for IFNin tuning the CD8 co-receptor during primary CD8 T cell activation both in vitro and in vivo.