Mel14+ CD4+ T cells from aged mice display functional and phenotypic characteristics of memory cells.
Aging is accompanied by an increased fraction of memory CD4+ T cells. Despite the fact that human memory cells have been reported to produce high levels of IL-2, studies in mice and man indicate an age-related decline in IL-2 production. In the present study, we examined whether these conflicting results depend on the activation pathway employed in a comparison of phenotypically distinct CD4+ T cells from young and aged mice. Our data indicate an age-related decline in IL-2 production by CD4+ T cells when the cells were stimulated with concanavalin A in the presence of accessory cells or the combination of immobilized anti-CD3 and soluble anti-CD28. However, when CD4+ T cells were only stimulated with immobilized anti-CD3, an age-related increase in IL-2 production was observed. This age-related increase in IL-2 could be attributed to the ability of CD4+ T cells from aged mice to produce IL-4 on this stimulation, since anti-IL-4 inhibited the IL-2 production in these cultures to levels found with cells from young mice. The addition of exogenous IL-4 greatly enhanced the IL-2 production of CD4+ T cells from young mice to levels far beyond that of the aged counterparts, emphasizing the dominant role of IL-4 in the induction of IL-2 stimulated with immobilized anti-CD3. No differences were observed in the activation requirements of Mel14- CD4+ T cells from young and aged mice.(ABSTRACT TRUNCATED AT 250 WORDS)
Dobber
R
R
Section of Immunology, Institute of Aging and Vascular Research TNO, Leiden, The Netherlands.
Tielemans
M
M
de Weerd
H
H
Nagelkerken
L
L
D000375:Aging / Q000276:immunology*; D000818:Animals; D017252:CD3 Complex / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D002352:Carrier Proteins / Q000096:biosynthesis; D015815:Cell Adhesion Molecules / Q000276:immunology; D002478:Cells, Cultured; D018960:Hyaluronan Receptors; D007156:Immunologic Memory / Q000276:immunology*; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis; D007376:Interleukin-2 / Q000096:biosynthesis; D015847:Interleukin-4 / Q000096:biosynthesis; D019041:L-Selectin; D008213:Lymphocyte Activation; D008297:Male; D051379:Mice; D008808:Mice, Inbred CBA; D011956:Receptors, Cell Surface / Q000096:biosynthesis; D016201:Receptors, Lymphocyte Homing / Q000096:biosynthesis
D017252:CD3 Complex; D002352:Carrier Proteins; D015815:Cell Adhesion Molecules; D018960:Hyaluronan Receptors; D007376:Interleukin-2; D011956:Receptors, Cell Surface; D016201:Receptors, Lymphocyte Homing; D018799:Intercellular Adhesion Molecule-1; D019041:L-Selectin; D015847:Interleukin-4