Impairment of CD3-dependent and CD3-independent activation pathways in CD4+ and in CD8+ T cells from old CBA/RIJ mice.
Stimulation of T cells from old mice with anti-CD3 antibodies resulted in a high variability of proliferative responses, which were 2- to 8-fold lower than the responses by T cells from young mice, even in the presence of exogenous rIL-2. Moreover, the CD4+ T cells from these old mice displayed a diminished capacity to produce IL-2 in response to anti-CD3. A partial explanation was found in the observation that T cells from the majority of old mice displayed a diminished expression of CD3 of variable intensity. However, after stimulation of the T cells with the combination of phorbol-12-myristate-13-acetate (PMA) and ionomycin to bypass CD3, 3 out of 6 old mice still exhibited 2-fold lower proliferative responses than T cells from young mice; IL-2 production by the CD4+ T cells was lower in all old mice tested. Comparison of CD4+ T cells and CD8+ T cells from old mice revealed a defective PMA/ionomycin response in both subsets, although this defect seemed more pronounced in CD4+ T cells when compared with the young counterparts. The diminished response of CD8+ T cells was accompanied by a diminished expression of the IL-2R alpha-chain. In contrast, old CD4+ T cells expressed rather higher levels of IL-2R alpha-chain than young CD4+ T cells. Altogether, multiple defects which are not necessarily the same in CD4+ and CD8+ T cells are responsible for defective T cell responses in old mice.
Hertogh-Huijbregts
A
A
Department of Immunology, Institute for Experimental Gerontology TNO, Rijswijk, The Netherlands.
Vissinga
C
C
Rozing
J
J
Nagelkerken
L
L
D000375:Aging / Q000276:immunology*; D000818:Animals; D000945:Antigens, Differentiation, T-Lymphocyte; D017252:CD3 Complex; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D016827:CD8 Antigens; D066298:In Vitro Techniques; D007376:Interleukin-2 / Q000096:biosynthesis / Q000494:pharmacology; D015759:Ionomycin / Q000494:pharmacology; D008213:Lymphocyte Activation / Q000187:drug effects; D008297:Male; D051379:Mice; D008808:Mice, Inbred CBA; D011948:Receptors, Antigen, T-Cell; D015375:Receptors, Interleukin-2 / Q000096:biosynthesis; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D000945:Antigens, Differentiation, T-Lymphocyte; D017252:CD3 Complex; D016827:CD8 Antigens; D007376:Interleukin-2; D011948:Receptors, Antigen, T-Cell; D015375:Receptors, Interleukin-2; D015759:Ionomycin; D013755:Tetradecanoylphorbol Acetate