FUNCTIONAL-PROPERTIES OF CD4(-) T-CELLS IN THE AGING IMMUNE-SYSTEM()CD28()

The aging immune system is characterized by a progressive decline in t he responsiveness to exogenous antigens and tumors in combination with a paradoxical increase in autoimmunity. From a clinical viewpoint, de ficiencies in antibody responses to exogenous antigens, such as vaccin es, have a major impact and may reflect intrinsic B cell defects or al tered performance of helper T cells. Here we describe that aging is as sociated with the emergence of an unusual CD4 T cell subset characteri zed by the loss of CD28 expression. CD28 is the major costimulatory mo lecule required to complement signaling through the antigen receptor f or complete T cell activation. CD4(+) CD28(-) T cells are long-lived, typically undergo clonal expansion in vivo, and react to autoantigens in vitro. Despite the deficiency of CD28, these unusual T cells remain functionally active and produce high concentrations of interferon-gam ma (IFN-gamma) and interleukin-2 (IL-2). The loss of CD28 expression i s correlated with a lack of CD40 ligand expression rendering these CD4 T cells incapable of promoting B cell differentiation and immunoglobu lin secretion. Aging-related accumulation of CD4(+) CD28(-) cells shou ld result in an immune compartment skewed towards autoreactive respons es and away from the generation of high-affinity B cell responses agai nst exogenous antigens. We propose that the emergence of CD28-deficien t CD4 T cells in the elderly can partially explain age-specific aberra tions in immune responsiveness. (C) 1998 Elsevier Science Ireland Ltd. All rights reserved.