Age-related defects in CD2 receptor-induced activation in human T-cell subsets.
It is well documented that the proliferative capacity of T cells declines with advancing age. There are, however, conflicting data as to the role of the accessory cell and whether or not this loss in responsiveness extends to all T-cell stimuli and to all T cells. We report here on the capacity of subpopulations of peripheral blood CD4+ T cells from the healthy aged to proliferate in response to anti-CD2 receptor-induced activation in the complete absence of accessory cells by using various exogenous cofactors as second signals. These costimulatory factors included phorbol 12-myristate 13-acetate (PMA), interleukin (IL)-1, IL-2, IL-6 and IL-7 and the monoclonal antibodies, anti-CD28 and anti-CD44. Under these conditions, the proliferative responsiveness of CD4+CD45RO+ T cells from the aged was found to be comparable to young control cells for all stimuli tested, except anti-CD2 plus IL-7. This suggests that signal transduction pathways involving CD2, except IL-7-mediated events, are essentially intact in 'old' memory CD4+ T cells. On the other hand, several cofactors, namely IL-2, IL-6, IL-7 and to a lesser extent IL-1 beta and PMA, failed to support adequately CD2-induced activation in 'old' CD4+CD45RA+ T cells suggesting severe and multiple signalling deficiencies in this subset.
Beckman
I
I
Department of Microbiology, Flinders Medical Centre, Adelaide, South Australia.
Shepherd
K
K
Firgaira
F
F
Ahern
M
M
D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000276:immunology*; D018801:CD2 Antigens / Q000276:immunology*; D018929:Cell Culture Techniques; D002455:Cell Division / Q000276:immunology; D005260:Female; D006801:Humans; D007378:Interleukins / Q000276:immunology; D017493:Leukocyte Common Antigens / Q000032:analysis; D008213:Lymphocyte Activation / Q000276:immunology*; D008297:Male; D016176:T-Lymphocyte Subsets / Q000276:immunology*
D018801:CD2 Antigens; D007378:Interleukins; D017493:Leukocyte Common Antigens