DECREASED PROLIFERATIVE CAPACITY AND INCREASED SUSCEPTIBILITY TO ACTIVATION-INDUCED CELL-DEATH IN LATE-PASSAGE HUMAN CD4(-CELL CLONES() TCR2(+) CULTURED T)

The growth characteristics in vitro of interleukin 2 (IL 2)-dependent human CD4(+) alpha beta-T cell receptor-positive helper T cell clones (TCC) were studied in relation to alterations in surface phenotype, cy tokine responsiveness, and susceptibility to activation-induced cell d eath (AICD). TCC derived from peripheral blood T cells had finite life spans averaging 33 population doublings (PD) with a recorded maximum l ifespan of 80 PD (n = 208). First analyses of the TCC were undertaken at ca. 25 PD, at which time all cells of all TCC expressed high intens ity CD45RO and low intensity CD45RA, as well as high intensity CD95 (f as) and MHC class II antigens. The expression of these molecules remai ned elevated throughout the proliferative lifespan of the clones, but for those TCC which were initially CD28(+) (the majority), the density of expression of the latter was diminished in most late-passage clone s. Concomitant with this, late-passage cells showed reduced responsive ness to CD28-mediated costimulation by CHO transfectants expressing hu man CD80 compared to early-passage cells. Additionally, the level of e xpression of a 2R gamma c and IL 7R chains was commonly reduced, as wa s the response to IL 2 and IL 7. Despite unchanged levels of fas expre ssion on TCC with time, late-passage cells were more susceptible to AI CD than early-passage cells. These observations further document funct ional and phenotypic alterations in long-term cultured human T helper cells, which may be considered as biomarkers of immunosenescence. This may contribute to an improved understanding of the mechanisms underly ing depressed T cell function in old age. Copyright (C) 1996 Elsevier Science Inc.