Damle N K, Doyle L V
Department of Immunology, CETUS Corporation, Emeryville, CA 94608.
J Immunol. 1989 Sep 15;143(6):1761-7.
Although both IL-2 and IL-4 can promote the growth of activated T cells, IL-4 appears to selectively promote the growth of those helper/inducer and cytolytic T cells which have been activated via their CD3/TCR complex. The present study examines the participation of CD28 and certain other T cell-surface molecules in inducing T cell responsiveness to IL-4. Purified small high density T cells were cultured in the absence of accessory cells with various soluble anti-human T cell mAb with or without soluble anti-CD3 mAb and their responsiveness to IL-4 was studied. None of the soluble anti-T cell mAb alone was able to induce T cell proliferation in response to IL-4. A combination of soluble anti-CD3 with anti-CD28 mAb but not with mAb directed at the CD2, CD5, CD7, CD11a/CD18, or class I MHC molecules induced T cell proliferation in response to IL-4. Anti-CD2 and anti-CD5 mAb enhanced and anti-CD18 mAb inhibited this anti-CD3 + anti-CD28 mAb-induced T cell response to IL-4. In addition, anti-CD2 in combination with anti-CD3 and anti-CD28 mAb induced modest levels of T cell proliferation even in the absence of exogenous cytokines. IL-1, IL-6, and TNF were each unable to replace either anti-CD3 or anti-CD28 mAb in the induction of T cell responsiveness to IL-4, but both IL-1 and TNF enhanced this response. The anti-CD3 + anti-CD28 mAb-induced response to IL-4 was exhibited only by cells within the CD4+CD29+CD45R- memory T subpopulation, and not by CD8+ or CD4+CD45R+ naive T cells. When individually cross-linked with goat anti-mouse IgG antibody immobilized on plastic surface, only anti-CD3 and anti-CD28 mAb were able to induce T cell proliferation. These results indicate that the CD3 and CD28 molecules play a crucial role in inducing T cell responsiveness to IL-4 and that the CD2, CD5, and CD11a/CD18 molecules influence this process.
虽然白细胞介素-2（IL-2）和白细胞介素-4（IL-4）都能促进活化T细胞的生长，但IL-4似乎能选择性地促进那些通过其CD3/TCR复合体被激活的辅助/诱导性T细胞和溶细胞性T细胞的生长。本研究检测了CD28和某些其他T细胞表面分子在诱导T细胞对IL-4反应性中的作用。纯化的小高密度T细胞在无辅助细胞的情况下，与各种可溶性抗人T细胞单克隆抗体（mAb）一起培养，同时加入或不加入可溶性抗CD3 mAb，并研究它们对IL-4的反应性。单独的可溶性抗T细胞mAb均不能诱导T细胞对IL-4产生增殖反应。可溶性抗CD3与抗CD28 mAb联合使用可诱导T细胞对IL-4产生增殖反应，而与针对CD2、CD5、CD7、CD11a/CD18或I类主要组织相容性复合体（MHC）分子的mAb联合使用则不能。抗CD2和抗CD5 mAb增强了这种抗CD3 +抗CD28 mAb诱导的T细胞对IL-4的反应，而抗CD18 mAb则抑制了这种反应。此外，抗CD2与抗CD3和抗CD28 mAb联合使用，即使在没有外源性细胞因子的情况下也能诱导适度水平的T细胞增殖。白细胞介素-1（IL-1）、白细胞介素-6（IL-6）和肿瘤坏死因子（TNF）在诱导T细胞对IL-4的反应性方面均不能替代抗CD3或抗CD28 mAb，但IL-1和TNF均增强了这种反应。抗CD3 +抗CD28 mAb诱导的对IL-4的反应仅在CD4+CD29+CD45R-记忆T亚群的细胞中表现出来，而在CD8+或CD4+CD45R+初始T细胞中则未表现出来。当单独与固定在塑料表面的山羊抗小鼠IgG抗体交联时，只有抗CD3和抗CD28 mAb能够诱导T细胞增殖。这些结果表明，CD3和CD28分子在诱导T细胞对IL-4的反应性中起关键作用，而CD2、CD5和CD11a/CD18分子影响这一过程。
