Interleukin-12 primes human CD4 and CD8 T cell clones for high production of both interferon-gamma and interleukin-10.
Interleukin-12 primes human CD4 and CD8 T cell clones for high production of both interferon-gamma and interleukin-10.
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DOI：
10.1084/jem.183.6.2559
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发表时间：
1996-06-01
影响因子：
15.3
通讯作者：
Trinchieri, G
中科院分区：
文献类型：
--
作者：
Gerosa, F;Paganin, C;Peritt, D;Paiola, F;Scupoli, MT;AsteAmezaga, M;Frank, I;Trinchieri, G
白细胞介素-12（IL-12）诱导辅助性T细胞1（Th 1）的分化，主要是通过其引发T细胞产生高干扰素-γ（IFN-γ）的能力。我们现在报道，在多克隆刺激的人外周血CD 4+和CD 8 + T细胞的有限稀释培养物中，在体外克隆扩增的前几天中IL-12的存在也诱导了高IL-10产生的稳定引发。这种效果在来自健康供体和HIV+患者的T细胞中得到了证实。在含有IL-12和IL-4的培养物中，需要IL-4的IL-4产生的引发最大。IL-4适度抑制IL-12诱导的IFN-γ的引发，但几乎完全抑制IL-10产生的引发。由记忆性CD 45 RO+细胞产生的一部分克隆，而不是由初始CD 45 RO-CD 4 + T细胞产生的克隆，即使在不存在IL-12和IL-4的情况下也产生IFN-γ、IL-10和IL-4的一些组合，这表明体内细胞因子引发;然而，当在扩增过程中存在IL-12时，实际上从CD 45 RO（-）或（+）细胞产生的所有CD 4+克隆都产生高水平的IFN-γ和IL-10。这些结果表明，每个Th 1型（IFN-γ）和Th 2型（IL-4和IL-10）细胞因子基因在人T细胞中是独立调节的，并且具有Th 1和Th 2细胞的细胞因子产生模式的T细胞之间的二分法不是由于免疫调节细胞因子的直接分化诱导作用，而是由于次级选择机制。细胞因子的特定组合诱导具有异常细胞因子产生模式的T细胞克隆的优势产生（例如，IFN-γ和IL-4或IFN-γ和IL-10），其也可以在一定比例的具有“记忆”表型的新鲜外周血T细胞或由其产生的克隆中发现，并且可以鉴定具有免疫调节功能的新Th亚群。
Interleukin-12 (IL-12) induces differentiation of T helper 1 (Th1) cells, primarily through its ability to prime T cells for high interferon-gamma (IFN-gamma) production. We now report that the presence of IL-12 during the first several days of in vitro clonal expansion in limiting dilution cultures of polyclonally stimulated human peripheral blood CD4+ and CD8+ T cells also induces stable priming for high IL-10 production. This effect was demonstrated with T cells from both healthy donors and HIV+ patients. Priming for IL-4 production, which requires IL-4, was maximum in cultures containing both IL-12 and IL-4. IL-4 modestly inhibited the IL-12-induced priming for IFN-gamma, but almost completely suppressed the priming for IL-10 production. A proportion of the clones generated from memory CD45RO+ cells, but not those generated from naive CD45RO- CD4+ T cells, produced some combinations of IFN-gamma, IL-10, and IL-4 even in the absence of IL-12 and IL-4, suggesting in vivo cytokine priming; virtually all CD4+ clones generated from either CD45RO(-) or (+) cells, however, produced high levels of both IFN-gamma and IL-10 when IL-12 was present during expansion. These results indicate that each Th1-type (IFN-gamma) and Th2-type (IL-4 and IL-10) cytokine gene is independently regulated in human T cells and that the dichotomy between T cells with the cytokine production pattern of Th1 and Th2 cells is not due to a direct differentiation-inducing effect of immunoregulatory cytokines, but rather to secondary selective mechanisms. Particular combinations of cytokines induce a predominant generation of T cell clones with anomalous patterns of cytokine production (e.g., IFN-gamma and IL-4 or IFN-gamma and IL-10) that can also be found in a proportion of fresh peripheral blood T cells with "memory" phenotype or clones generated from them and that may identify novel Th subsets with immunoregulatory functions.
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影响因子：
15.3
作者：
Croft, Michael;Carter, Laura;Swain, Susan L.;Dutton, Richard W.
通讯作者：
Dutton, Richard W.
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影响因子：
15.3
作者：
Heinzel, F P;Schoenhaut, D S;Rerko, R M;Rosser, L E;Gately, M K
通讯作者：
Gately, M K
影响因子：
15.3
作者：
D'Andrea, A;Aste-Amezaga, M;Valiante, N M;Ma, X;Kubin, M;Trinchieri, G
通讯作者：
Trinchieri, G
影响因子：
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作者：
COHEN, SBA;KATSIKIS, PD;FELDMANN, M
通讯作者：
FELDMANN, M
影响因子：
15.3
作者：
Chehimi, J;Starr, S E;Frank, I;D'Andrea, A;Ma, X;MacGregor, R R;Sennelier, J;Trinchieri, G
通讯作者：
Trinchieri, G