Diversity of clonal T cell proliferation is mediated by differential expression of CD152 (CTLA-4) on the cell surface of activated individual T lymphocytes
Diversity of clonal T cell proliferation is mediated by differential expression of CD152 (CTLA-4) on the cell surface of activated individual T lymphocytes
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DOI：
10.4049/jimmunol.171.7.3459
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发表时间：
2003-10-01
影响因子：
4.4
通讯作者：
Brunner-Weinzierl, MC
中科院分区：
文献类型：
--
作者：
Maszyna, F;Hoff, H;Brunner-Weinzierl, MC
CD152(CTLA-4)结合在T细胞活化过程中的抑制作用已经被描述。到目前为止，这种影响只能与群体水平的CD152表达相关，因为CD152在细胞表面的表达太低，不能用传统的免疫荧光在单细胞水平上进行评估。在这项研究中，我们使用磁性荧光脂质体对表达表面CD152的CD4(+)T细胞进行免疫荧光检测，结果表明，尽管几乎所有细胞都表达细胞内CD152，但在任何给定的时间点，只有一小部分激活的T细胞表达表面CD152。表面CD152(+)T细胞在体外一次或二次激活后表现出相似的动力学特征。然而，在二次激活过程中，激活48h后表面CD152(+)T细胞的频率是第二次激活时的2倍。CD152的表面表达与活化T细胞的增殖史无关。T细胞对CD152表面表达的指示依赖于自激活开始以来所经过的时间，最大值在48h，并且需要不到12h的Ag暴露。CD152(-)T细胞，当通过细胞分选分离并重新刺激时，继续增殖。CD152阻断对其增殖无影响。分离的表面CD152(+)T细胞在重新刺激时不会增殖，除非CD152被阻断。因此，CD152直接和自主地作用于个体激活和增殖的T淋巴细胞。由于CD152在活化的Th细胞表面的异质性表达，CD152可能使T细胞的应答多样化。
Inhibitory effects of CD152 (CTLA-4) engagement during T cell activation have been described. To date, such effects could only be correlated to CD152 expression at the population level because expression of CD152 on the cell surface is too low to be assessed by conventional immunofluorescence on the single cell level. In this study, we use magnetofluorescent liposomes for the immunofluorescent detection of surface CD152-expressing CD4(+) T cells and show that, despite the fact that nearly all cells express intracellular CD152, only a fraction of 12% of activated T cells expresses surface CD152 at any given time point. Surface CD152(+) T cells appear with similar kinetics after primary or secondary activation in vitro. However, the frequency of surface CD152(+) T cells 48 h postactivation is 2-fold higher during secondary activation. Surface expression of CD152 is independent of the proliferative history of an activated T cell. Instruction of T cells for surface expression of CD152 rather depends on the time elapsed since the onset of activation, with a maximum at 48 h, and requires less than 12 h of Ag exposure. CD152(-) T cells, when isolated by cell sorting and restimulated, continue to proliferate. CD152 blockade has no effect on their proliferation. Isolated surface CD152(+) T cells do not proliferate upon restimulation unless CD152 is blocked. CD152 thus acts directly and autonomously on individual activated and proliferating T lymphocytes. Due to its heterogeneous expression on the cell surface of activated Th cells, CD152 might diversify the T cell response.