期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2008
卷号：105
期号：45
页码：17475-17480
DOI：10.1073/pnas.0809549105
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：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 IFN-{gamma} and IL-4 exert opposing effects on the expression of CD8{alpha} 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 IFN-{gamma} or IFN-{gamma}R gene. When WT or IFN-{gamma}-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-/-{gamma}c-/- mice, CD8 levels were highest on WT donor cells from mice that received the control tumor and lowest on IFN-{gamma}-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 IFN-{gamma} in tuning the CD8 co-receptor during primary CD8+ T cell activation both in vitro and in vivo.
关键词：CD8low ; co-receptor tuning ; T cell activation ; cytotoxic T lymphocytes ; cytokines
