Gillis S, Kozak R, Durante M, Weksler M E
J Clin Invest. 1981 Apr;67(4):937-42. doi: 10.1172/jci110143.
Human lymphocytes from elderly and young donors were cultured with phytohemagglutinin (PHA) or concanavalin A. Cultures from old donors produced less T cell growth factor (TCGF) and incorporated less tritiated thymidine (3H-Tdr) than did similar cultures from young donors in the presence of either mitogen. Furthermore, the response of lymphocytes from elderly donors to TCGF was impaired. Thus, PHA-activated T cells from aged donors showed no increase tritiated thymidine incorporation when incubated with exogenous human TCGF. In contrast, addition of exogenous human TCGF to PHA-activated peripheral blood leukocytes from younger individuals increased tritiated thymidine incorporation by 30-50%. The impaired response to TCGF was associated with decreased binding of TCGF by PHA-activated cells from old donors. TCGF production or responsiveness was not associated with the presence of "suppressor" activity in elderly T cell preparations. These studies suggest a possible molecular mechanism for the impaired proliferative response of elderly human T cells. These data lend support to the hypothesis that defects in the capacity to either produce or respond to TCGF may be a fundamental cause of immune deficiency.
将老年和年轻供体的人淋巴细胞与植物血凝素（PHA）或刀豆球蛋白A一起培养。在存在任何一种有丝分裂原的情况下，来自老年供体的培养物产生的T细胞生长因子（TCGF）较少，并且掺入的氚化胸腺嘧啶核苷（3H-Tdr）比来自年轻供体的类似培养物少。此外，老年供体的淋巴细胞对TCGF的反应受损。因此，来自老年供体的PHA激活的T细胞在与外源性人TCGF孵育时，氚化胸腺嘧啶核苷掺入没有增加。相反，向来自年轻个体的PHA激活的外周血白细胞中添加外源性人TCGF可使氚化胸腺嘧啶核苷掺入增加30%-50%。对TCGF反应受损与来自老年供体的PHA激活细胞对TCGF的结合减少有关。TCGF的产生或反应性与老年T细胞制剂中“抑制”活性的存在无关。这些研究提示了老年人类T细胞增殖反应受损的一种可能分子机制。这些数据支持了这样一种假说，即产生或对TCGF反应的能力缺陷可能是免疫缺陷的根本原因。
