Type IIFN negatively regulates CD8+ T cell responses through IL-10-Producing CD4+ T regulatory 1 cells
Type IIFN negatively regulates CD8+ T cell responses through IL-10-Producing CD4+ T regulatory 1 cells
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DOI：
10.4049/jimmunol.174.1.99
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发表时间：
2005-01-01
影响因子：
4.4
通讯作者：
Reimann, J
中科院分区：
文献类型：
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作者：
Dikopoulos, N;Bertoletti, A;Reimann, J
I型干扰素对T细胞反应的多效性免疫调节作用正在出现。我们在IFN- β (IFN- β(-/-))或I型IFN受体（IFNAR(-/-)）缺陷小鼠中使用疫苗诱导的抗病毒CD8(+) T细胞反应来研究I型IFN不受伴随病毒感染干扰的免疫调节作用。与正常B6小鼠相比，IFNAR（-/-）或ifn - β(-/-)小鼠的肝脏和脾脏中CD4（+）和CD8(+) T细胞数量正常，CD25(+)FoxP3(+) T调节（T(R)）细胞数量正常。在以肽或dna为基础的疫苗接种后，IFNAR(-/)-或ifn - β(-/-)小鼠中产生的CD8(+) T细胞特异性针对不同i类限制性表位的数量是正常动物的两倍。ifn - γ和tnf - α的产生和特异性CD8+ T细胞克隆扩增在正常小鼠和敲除小鼠中是相似的。在正常、IFNAR（-/-）或ifn - β(-/-)小鼠中，CD25(+)FoxP3(+) T(R)细胞下调疫苗引发的CD8(+) T细胞反应的程度相当。体内低剂量ifn - α或ifn - β （500-10(3) U/小鼠）下调CD8(+) T细胞的启动。体外或体内多克隆或特异性刺激后，IFNAR-和ifn - β缺陷小鼠产生2- to - Mold低数量的产生il -10的CD4+ T细胞。因此，CD8(+) T细胞反应受到CD25(+)FoxP3(+) T细胞和CD4(+)IL-10(+) T（R1）细胞的阴性控制，但只有后者T细胞的发育取决于I型IFN。
Pleiotropic, immunomodulatory effects of type I IFN on T cell responses are emerging. We used vaccine-induced, antiviral CD8(+) T cell responses in IFN-beta (IFN-beta(-/-))- or type I IFN receptor (IFNAR(-/-))-deficient mice to study immunomodulating effects of type I IFN that are not complicated by the interference of a concomitant virus infection. Compared with normal B6 mice, IFNAR(-/-) or IFN-beta(-/-) mice have normal numbers of CD4(+) and CD8(+) T cells, and CD25(+)FoxP3(+) T regulatory (T(R)) cells in liver and spleen. Twice as many CD8(+) T cells specific for different class I-restricted epitopes develop in IFNAR(-/)- or IFN-beta(-/-) mice than in normal animals after peptide- or DNA-based vaccination. IFN-gamma and TNF-alpha production and clonal expansion of specific CD8+ T cells from normal and knockout mice are similar. CD25(+)FoxP3(+) T(R) cells down-modulate vaccine-primed CD8(+) T cell responses in normal, IFNAR(-/-), or IFN-beta(-/-) mice to a comparable extent. Low IFN-alpha or IFN-beta doses (500-10(3) U/mouse) down-modulate CD8(+) T cells priming in vivo. IFNAR- and IFN-beta-deficient mice generate 2- to Mold lower numbers of IL-10-producing CD4+ T cells after polyclonal or specific stimulation in vitro or in vivo. CD8(+) T cell responses are thus subjected to negative control by both CD25(+)FoxP3(+) T, cells and CD4(+)IL-10(+) T(R1) cells, but only development of the latter T, cells depends on type I IFN.