Differential expression of p53 tumor suppressor protein and IL-2 in activated T cells from elderly humans.
Aging is associated with a decline in T cell proliferative responses and aberrations in cytokine production. In the present study, we examined if aging might alter the expression of the tumor-suppressor protein p53 and the retinoblastoma susceptibility gene product (Rb) as well as the levels of Bcl-2 in resting and activated human T cells. No significant differences were observed in the basal levels of p53 protein among resting T cells from young and elderly humans. After stimulation with anti-CD3 monoclonal antibody (mAb) OKT3 and phorbol myristate acetate (PMA), T cells from young humans exhibited severalfold increases in p53 protein expression compared with resting T cells. By contrast, T cells from a substantial portion of elderly humans failed to demonstrate significant increases in p53 in response to anti-CD3 plus PMA. No age-related alterations in the levels of Rb or Bcl-2 proteins were observed in resting or anti-CD3/PMA-stimulated T cells. To delineate whether the age-related reductions in p53 expression might be linked to decreased interleukin-2 (IL-2) production, we compared the expression of p53 and IL-2 in anti-CD3/PMA-stimulated T cells from elderly people. The results showed that impaired induction of p53 expression in activated T cells from certain elderly people could be observed without considerable impairments in IL-2 production. These observations suggest that age-related reductions in T cell expression of p53 may contribute to the decline of T cell competence independent of the impairments in IL-2 production.
VanAman
S E
SE
Department of Internal Medicine, The William H. Davis Medical Research Center, The Ohio State University, Columbus 43210, USA.
Whisler
R L
RL
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001481:Basal Metabolism; D002478:Cells, Cultured; D005260:Female; D006801:Humans; D007376:Interleukin-2 / Q000096:biosynthesis*; D008213:Lymphocyte Activation; D008297:Male; D008875:Middle Aged; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis; D018709:Statistics, Nonparametric; D013601:T-Lymphocytes / Q000378:metabolism*; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis*
D007376:Interleukin-2; D019253:Proto-Oncogene Proteins c-bcl-2; D016159:Tumor Suppressor Protein p53