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

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 `agedʹ and `youngʹ 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 `agedʹ 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.