Age-related impairment of T cell proliferative responses related to the decline of CD28+ T cell subsets

CD28 T细胞 CD86 植物血凝素 幼稚T细胞 免疫学 白细胞介素2 T淋巴细胞 生物 抗原 细胞因子 内分泌学 内科学 淋巴细胞 医学 免疫系统 T细胞受体
作者
Cosimo Tortorella,M. P. Loria,Giuseppina Piazzolla,Hendrik Schulze‐Koops,Peter E. Lipsky,Emilio Jirillo,Salvatore Antonaci
出处
期刊:Archives of Gerontology and Geriatrics [Elsevier BV]
卷期号:26 (1): 55-70 被引量:17
标识
DOI:10.1016/s0167-4943(97)00033-2
摘要

The impairment of phytohaemagglutinin-triggered lymphocyte proliferation represents a prominent immunologic abnormality in elderly individuals. To assess whether the reduced function is related to a CD28/B7 signalling deficiency, purified T lymphocytes and antigen presenting cells (APCs) were analyzed for their phenotypic profile and/or functional capacities. T cell responses to immobilized OKT3 monoclonal antibodies (mAb) or a combination of anti-CD2 mAb and phorbol esters were unaffected in old subjects when compared to the younger counterpart. In contrast, CD28 costimulation in the presence of OKT3 or anti-CD2 mAb, gave rise to significantly diminished T cell proliferative responses. These findings correlated with a marked decline of CD28+ T cell frequency, which mainly involved the CD4−CD45RO− cell subset. The defect in CD28 expression could not be reversed by T cell stimulation, as a comparable increase in CD28 levels occurred in both `aged' and `young' T cells after in vitro activation. Moreover, the elderly group did not exhibit a reduction of interleukin (IL)-2 synthesis, as assessed at 24 h of culture, regardless of the stimulant used. Finally, B7.2 (CD86) expression by `aged' CD14+ APCs was unaffected in both resting and interferon-γ activated cells. These results suggest that an intrinsic defect in CD28 expression might in part account for the age-related decline of T cell proliferative responses.
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