Autologous mixed lymphocyte reaction in man. XX. The cellular and molecular basis of deficient T-T AMLR in aging humans.
In the T-T AMLR, suppressor functions are generated, and because in human aging a deficiency of suppressor function has been observed, we examined the T-T AMLR in aging humans. Non-T cells were irradiated and used as stimulators against fresh autologous responder T cells to generate activated T cells (TA). TA cells were irradiated and used as stimulators against fresh autologous responder T cells (T-TA AMLR), CD4+ cells (CD4-TA AMLR), or CD8+ cells (CD8-TA AMLR) in the presence or absence of recombinant interleukin 2 (rIL-2). T cells from young and aging subjects were stimulated with phytohemagglutinin and examined for the expression of IL-2 receptors (IL-2R) and transferrin receptors. A significant decrease in T-TA, CD4-TA, and CD8-TA AMLR was observed in aging humans when compared with simultaneously studied sex-matched young controls. In vitro addition of rIL-2 resulted in an enhanced AMLR in both young and aging subjects; however, the total [3H]thymidine incorporation by T cells and T-cell subsets from aging in the presence of rIL-2 was lower than that of young subjects' T cells and T-cell subsets in the presence of rIL-2. The net increase (over the baseline values) in [3H]thymidine incorporation in T-TA and CD8-TA by rIL-2 was significantly less in the aging group when compared to the young group. In contrast, the rIL-2-induced net increase in [3H]thymidine incorporation in CD4-TA AMLR in both groups was comparable. T cells expressing IL-2R and transferrin receptors were of similar proportions in two groups. These data show a deficiency of the T-T AMLR in aging humans that appears to be, at least in part, due to deficient response to rIL-2. This deficiency of the T-T AMLR might be responsible for deficient suppressor activity, hyperimmunoglobulinemia, and the presence of autoantibodies in aging humans.
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000276:immunology*; D003602:Cytotoxicity, Immunologic; D005260:Female; D006801:Humans; D007376:Interleukin-2 / Q000032:analysis; D007959:Lymphocyte Culture Test, Mixed; D008297:Male; D011990:Receptors, Transferrin / Q000032:analysis; D013601:T-Lymphocytes / Q000145:classification / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*
D007376:Interleukin-2; D011990:Receptors, Transferrin