Differential effects of CD4 and CD8 engagement on the development of cytokine profiles of murine CD4+ and CD8+ T lymphocytes
Differential effects of CD4 and CD8 engagement on the development of cytokine profiles of murine CD4+ and CD8+ T lymphocytes
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DOI：
10.1046/j.1365-2567.2000.00971.x
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发表时间：
2000-03-01
期刊：
影响因子：
6.4
通讯作者：
Kelso, A
中科院分区：
文献类型：
--
作者：
Campbell, SB;Komata, T;Kelso, A
使用一种无抗原呈递细胞的简单培养系统，来检测固定化的抗淋巴细胞功能相关抗原 - 1（LFA - 1）（CD11a）、CD28以及CD4或CD8抗体调节正常小鼠淋巴结CD4⁺和CD8⁺ T细胞对固定化抗CD3抗体和白细胞介素 - 2（IL - 2）反应的能力。所有抗体都增强了对限量抗CD3抗体的增殖反应。无论用于启动的共激活抗体如何，CD4⁺和CD8⁺细胞在原代和传代培养中都产生大量的IL - 3和干扰素 - γ（IFN - γ）。相比之下，在CD4⁺细胞培养中，抗CD4与抗CD3抗体的组合比任何其他抗体组合刺激产生的IL - 4滴度显著更高。这种依赖CD4的IL - 4反应在初始（CD44低表达）表型的CD4⁺ T细胞中被诱导，其强度与外源性IL - 4诱导的反应相似，但与后者不同的是，它与IL - 3合成增加无关。在CD8⁺细胞上未观察到抗CD8抗体的类似作用：尽管外源性IL - 4可诱导CD8⁺细胞产生IL - 4，但在与抗CD8或任何其他抗体共激活后未检测到。我们得出结论，抗CD4抗体是分泌IL - 4的CD4⁺ T细胞的强效诱导剂，其作用可与抗CD8抗体对CD8⁺ T细胞的作用以及IL - 4对任一亚群的作用区分开来。
A simple culture system devoid of antigen-presenting cells was used to examine the ability of immobilized antibodies to lymphocyte function-associated antigen-1 (LFA-1) (CD11a), CD28 and CD4 or CD8 to modulate the responses of normal murine CD4(+) and CD8(+) lymph node T cells to immobilized anti-CD3 antibody and interleukin-2 (IL-2). All the antibodies enhanced proliferative responses to limiting anti-CD3 antibody. Both CD4(+) and CD8(+) cells produced substantial titres of IL-3 and interferon-gamma (IFN-gamma) in primary and secondary cultures regardless of the coactivating antibodies used for priming. By contrast, the combination of anti-CD4 with anti-CD3 antibody stimulated significantly higher titres of IL-4 than any other antibody combination in cultures of CD4(+) cells. This CD4-dependent IL-4 response was induced in CD4(+) T cells of naive (CD44(low)) phenotype and was similar in magnitude to the response induced by exogenous IL-4 but, unlike the latter, was not associated with elevated IL-3 synthesis. A comparable effect of anti-CD8 antibodies on CD8(+) cells was not observed: although IL-4 production by CD8(+) cells was induced by exogenous IL-4, it was not detected following coactivation with anti-CD8 or any other antibodies. We conclude that anti-CD4 antibody is a potent inducer of IL-4-secreting CD4(+) T cells whose effects can be distinguished from those of anti-CD8 antibody on CD8(+) T cells and from those of IL-4 on either subset.