Conlon K C, Ochoa A C, Kopp W C, Ortaldo J R, Urba W J, Longo D L, Young H A
Laboratory of Experimental Immunology, Program Resources, Inc./DynCorp, Frederick, MD.
J Immunol. 1992 Nov 15;149(10):3278-89.
Treatment of T lymphocytes with antibodies directed against the T cell receptor CD3 complex results in cellular activation that can be augmented by costimulation through other cell surface receptors. The activities of anti-CD3-stimulated human CD4+ PBL were compared to anti-CD3 plus anti-CD2-, anti-CD4-, or anti-CD11a (LFA-1)-stimulated cells. [3H]thymidine incorporation, lymphokine receptor expression, expansion of cell numbers, and lymphokine mRNA and protein were measured. Forty-eight hours after activation, costimulated CD4+ cells demonstrated increased numbers of cells positive for surface IL-2R alpha-chain, IL-2R beta-chain, IFN-gamma receptors, and TNF-alpha receptors. By day 6, costimulated cells exhibited a sevenfold greater expansion in cell numbers compared to cells stimulated with anti-CD3 alone. Anti-CD3 plus anti-CD11a stimulation consistently induced the highest secretion of IL-2 and IFN-gamma, whereas variation in secretion of TNF-alpha and IL-4 between different donors was noted. Analysis of lymphokine receptor mRNA demonstrated increased levels of mRNA for IL-2R alpha-chain and IFN-gamma receptor that preceded the phenotypic changes on the cell surface. In contrast, levels of IL-2R beta-chain and the TNF-alpha receptor mRNA decreased after stimulation. Amounts of IL-2, IL-4, and TNF-alpha, but not IFN-gamma, secreted also correlated with the levels of mRNA measured in the cells. Although costimulation through CD2, CD4, or LFA-1 appeared equally effective for the induction of the lymphokine receptors, these additional stimuli had a different impact on lymphokine secretion. These results indicate that specific control of lymphokine secretion and receptor induction can be another function of the CD2, CD4, and CD11a cell surface receptors. This control is evident at both transcriptional and post-transcriptional levels.
用针对T细胞受体CD3复合物的抗体处理T淋巴细胞会导致细胞活化，这种活化可通过其他细胞表面受体的共刺激作用而增强。将抗CD3刺激的人CD4⁺外周血淋巴细胞（PBL）的活性与抗CD3加抗CD2、抗CD4或抗CD11a（淋巴细胞功能相关抗原-1，LFA-1）刺激的细胞进行比较。测定了[³H]胸腺嘧啶核苷掺入、淋巴因子受体表达、细胞数量扩增以及淋巴因子mRNA和蛋白水平。活化48小时后，共刺激的CD4⁺细胞表面IL-2Rα链、IL-2Rβ链、IFN-γ受体和TNF-α受体阳性细胞数量增加。到第6天，与仅用抗CD3刺激的细胞相比，共刺激的细胞数量扩增了7倍。抗CD3加抗CD11a刺激始终诱导出最高水平的IL-2和IFN-γ分泌，而不同供体之间TNF-α和IL-4分泌存在差异。淋巴因子受体mRNA分析显示，IL-2Rα链和IFN-γ受体mRNA水平在细胞表面表型变化之前就已升高。相反，刺激后IL-2Rβ链和TNF-α受体mRNA水平下降。分泌的IL-2、IL-4和TNF-α（但不包括IFN-γ）的量也与细胞中测得的mRNA水平相关。尽管通过CD2、CD4或LFA-1的共刺激对于诱导淋巴因子受体似乎同样有效，但这些额外的刺激对淋巴因子分泌有不同的影响。这些结果表明，对淋巴因子分泌和受体诱导的特异性调控可能是CD2、CD4和CD11a细胞表面受体的另一功能。这种调控在转录和转录后水平均很明显。
