Age-related defects in Th1 and Th2 cytokine production by human T cells can be dissociated from altered frequencies of CD45RA+ and CD45RO+ T cell subsets.
The present study investigated whether age-related changes in the production of Th1 and Th2 cytokines by human T cells might be linked to altered frequencies of naive (CD45RA+) and memory (CD45RO+) T cell subsets. T cells from healthy elderly humans (n = 32) stimulated with anti-CD3epsilon monoclonal antibody OKT3 plus PMA produced significantly lower levels of IL-2 and IFNgamma (Th1 type) and of IL-4 (Th2 type) cytokines compared with T cells from young subjects. Although considerable heterogeneity was observed in the levels of cytokines produced by activated T cells from elderly individuals, linear regression analysis failed to demonstrate any significant shift in Th1 to Th2 type cytokine profiles of human T cells during aging. Sufficient T cells were available from eighteen elderly subjects to quantitate the 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 decreases in the frequencies of naive T cells with reciprocal increases in memory 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 normal frequencies of naive/memory T cells exhibited decreases in cytokine production comparable to the reductions observed for elderly donors with alterations in the frequencies of naive/memory T cells. These findings suggest that age-related defects in Th1 and Th2 cytokine production cannot be attributed entirely to alterations in the frequencies of naive/memory T cell subsets and point toward intrinsic aberrancies within human T cell cytokine networks during aging.
Karanfilov
C I
CI
Department of Internal Medicine, The William H. Davis Medical Research Center, The Ohio State University, Columbus 43210-1228, USA.
Liu
B
B
Fox
C C
CC
Lakshmanan
R R
RR
Whisler
R L
RL
D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000276:immunology*; D002478:Cells, Cultured; D005260:Female; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis*; D007376:Interleukin-2 / Q000096:biosynthesis*; D015847:Interleukin-4 / Q000096:biosynthesis*; D017493:Leukocyte Common Antigens / Q000276:immunology*; D008297:Male; D016176:T-Lymphocyte Subsets / Q000166:cytology / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology*; D018418:Th2 Cells / Q000276:immunology*
D007376:Interleukin-2; D015847:Interleukin-4; D007371:Interferon-gamma; D017493:Leukocyte Common Antigens