Graham Pawelec ¹, Ed Remarque ², Yvonne Barnett ³, Rafael Solana ⁴

1 University of Tübingen, Tübingen, FRG ², University of Leiden, Leiden, Holland ³, University of Ulster, Coleraine, Northern Ireland ⁴, University of Córdoba, Córdoba, Spain

Received 12/29/97 Accepted 1/5/97

2. INTRODUCTION

Scientific progress in immunosenescence research in general points more and more to a clinical relevance in man, although many areas remain controversial. The term immunosenescence designates that deterioration of immune function seen in the elderly which is believed to manifest in the increased susceptibility to cancer, autoimmune phenomena and infectious disease of the aged. There is increasingly good empirical evidence at least for the latter of these, showing that immunosenescence is clinically relevant for protection against infectious disease in the elderly. This suggests that failing immunity results in increased incidence of those diseases that the immune system evolved to protect against, ie. infectious diseases. Healthy life could be extended by preventing these infections using interventions designed to prevent, ameliorate or reverse immunosenescence. Because the immune response is guided by T cells which must undergo extensive clonal proliferation on contact with antigen in primary responses and repeated clonal expansion for memory responses, replicative senescence may be particularly important for T cells. Memory responses and effective vaccination may be especially affected by T cell replicative senescence. Proliferative lifespans and replicative senescence have been extensively studied in certain tissues, especially fibroblasts, but relatively little is known about the behavior of T cells and the molecular biology of their growth control and senescence. The control of lymphocyte aging, proliferation, costimulation, apoptosis induction and memory cell maintenance at the cellular and molecular level in vitro can be studied using cultured human T cells. T cell clones in vitro could therefore provide a potential model to study "longitudinal" age-associated changes during clonal expansion and eventual replicative exhaustion. This review attempts to bring together recent publications in the area of T cell immunosenescence and to act as a resource for investigators from this and other fields.