title: Age-related impairment of T cell proliferative responses related to the decline of CD28+ T cell subsets.
abstract: 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-gamma 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.
authors.affiliation: Department of Internal Medicine, Immunology and Infectious Diseases, University of Bari Medical School, Policlinico, 70124 Bari, Italy. allerg1@cimedoc.uniba.it
authors.forename: C
authors.initials: C
authors.lastname: Tortorella
authors.forename: M P
authors.initials: MP
authors.lastname: Loria
authors.forename: G
authors.initials: G
authors.lastname: Piazzolla
authors.forename: H
authors.initials: H
authors.lastname: Schulze-Koops
authors.forename: P E
authors.initials: PE
authors.lastname: Lipsky
authors.forename: E
authors.initials: E
authors.lastname: Jirillo
authors.forename: S
authors.initials: S
authors.lastname: Antonaci