CD4pos, NK1.1pos T cells promptly produce interleukin 4 in response to in vivo challenge with anti-CD3.
CD4pos, NK1.1pos T cells promptly produce interleukin 4 in response to in vivo challenge with anti-CD3.
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DOI：
10.1084/jem.179.4.1285
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发表时间：
1994-04-01
期刊：
影响因子：
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通讯作者：
Paul WE
中科院分区：
文献类型：
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作者：
Yoshimoto T;Paul WE
注射抗-CD 3抗体引起脾细胞中白细胞介素（IL）-4、IL-2和干扰素γ（IFN-γ）mRNA的迅速表达。抗CD 3的最佳诱导剂量为1.33 μ g/只动物;在30 min时首次观察到淋巴因子mRNA，在90 min时达到峰值，在4 h时检测不到（对于IL-4）或显著下降。从90分钟前注射抗CD 3的小鼠脾脏收获的细胞分泌IL-4、IL-2和IFN-γ，而无需进一步刺激。相比之下，在体外刺激与抗CD 3的脾细胞悬液或脾碎片从noninjected供体未能引起迅速生产的IL-4，即使在24小时的刺激，IL-4的产生量在这样的细胞是远远低于1小时内分泌的脾细胞悬液或脾碎片从小鼠注射抗CD 3 90分钟前。用抗IL-4抗体或IFN-γ或肿瘤生长因子β预处理不抑制抗CD 3注射小鼠脾细胞产生IL-4，用IL-4处理也不增强。相比之下，CTLA-4免疫球蛋白（IG）治疗明显减少了体内抗CD 3抗体产生的IL-4，表明涉及CD 28（或相关分子）的细胞相互作用在刺激中很重要。细胞分选分析表明，体内注射抗CD 3后产生IL-4的细胞高度富集于具有白细胞粘附分子-1（LECAM-1）dull、CD 44 bright、CD 45 RB dull、NK1.1 pos表型的CD 4 pos细胞。事实上，CD 4pos、NK1.1pos细胞的小群体具有该群体的绝大多数IL-4产生活性。注射葡萄球菌肠毒素B也引起IL-4 mRNA的迅速诱导;主要负责产生IL-4 mRNA的细胞也具有CD 4 pos、NK 1.1 pos的表型。这些结果表明，这种罕见的T细胞群体可能能够在免疫应答开始时分泌IL-4，因此可能通过提供IL-4的来源来调节幼稚T细胞的引发模式，以促进T细胞辅助2样IL-4产生细胞的发育。
Injection of anti-CD3 antibodies causes prompt expression of interleukin (IL)-4, IL-2, and interferon gamma (IFN-gamma) mRNA among spleen cells. The optimal dose of anti-CD3 for such induction was 1.33 microgram/animal; lymphokine mRNA was first observed at 30 min, peaked at 90 min, and was undetectable (for IL-4) or had declined markedly by 4 h. Cells harvested from spleens of mice injected with anti-CD3 90 min earlier secreted IL-4, IL-2, and IFN-gamma without further stimulation. By contrast, in vitro stimulation with anti-CD3 of spleen cell suspensions or splenic fragments from noninjected donors failed to cause prompt production of IL-4 and, even after 24 h of stimulation, the amount of IL-4 produced in such cells was substantially less than that secreted within 1 h by spleen cell suspensions or splenic fragments from mice injected with anti-CD3 90 min earlier. Production of IL-4 by spleen cells from anti-CD3-injected mice was not inhibited by pretreatment with anti-IL-4 antibody or with IFN-gamma or tumor growth factor beta nor enhanced by treatment with IL-4. By contrast, CTLA-4 immunoglobulin (Ig) treatment clearly diminished IL-4 production in response to in vivo anti-CD3, indicating that cellular interactions involving CD28 (or related molecules) were important in stimulation. Cell sorting analysis indicated that the cells that produced IL-4 in response to in vivo injection of anti-CD3 were highly enriched in CD4pos cells with the phenotype leukocyte cell adhesion molecule-1 (LECAM-1)dull, CD44bright, CD45RBdull, NK1.1pos. Indeed, the small population of CD4pos, NK1.1pos cells had the great majority of the IL-4- producing activity of this population. Injection with Staphylococcal enterotoxin B also caused prompt induction of IL-4 mRNA; the cells that were principally responsible for production also had the phenotype of CD4pos, NK1.1pos. These results suggest that possibility that this rare population of T cells may be capable of secreting IL-4 at the outset of immune responses and thus may act to regulate the pattern of priming of naive T cells, by providing a source of IL-4 to favor the development of T cell helper 2-like IL-4-producing cells.