Age-related defects in Th1 and Th2 cytokine production by human T cells can be dissociated from altered frequencies of CD45RA(+) and CD45RO(+) T cellsubsets

The present study investigated whether age-related changes in the productio n of Th1 and Th2 cytokines by human T cells might be linked to altered freq uencies of naive (CD45RA(+)) and memory (CD45RO(+)) T cell subsets. T cells from healthy elderly humans (n=32) stimulated with anti-CD3 epsilon monocl onal antibody OKT3 plus PMA produced significantly lower levels of IL-2 and IFN gamma (Th1 type) and of IL-4 (Th2 type) cytokines compared with T cell s from young subjects. Although considerable heterogeneity was observed in the levels of cytokines produced by activated T cells from elderly individu als, linear regression analysis failed to demonstrate any significant shift in Th1 to Th2 type cytokine profiles of human T cells during aging. Suffic ient T cells were available from eighteen elderly subjects to quantitate th e levels of cytokine production in parallel with flow cytometry analysis of the frequencies of CD45RA(+) naive and CD45RO(+) memory T cells. Compared with the group of young subjects, the elderly group exhibited significant d ecreases in the frequencies of naive T cells with reciprocal increases in m emory T cells. However, defects in Th1 and Th2 cytokine production were not significantly correlated with altered frequencies of naive/memory T cells among elderly individuals. In addition, those elderly individuals with norm al frequencies of naive/memory T cells exhibited decreases in cytokine prod uction comparable to the reductions observed for elderly donors with altera tions in the frequencies of naive/memory T cells. These findings suggest th at age-related defects in Th1 and Th2 cytokine production cannot be attribu ted entirely to alterations in the frequencies of naive/memory T cell subse ts and point toward intrinsic aberrancies within human T cell cytokine netw orks during aging. (C) 1999 Published by Elsevier Science Ireland Ltd. All rights reserved.