Transcriptional Control of IL-2 and IL-4 in T Cells of Young and Old Mice

Abstract

CD4+ T cells of aged compared to young subjects are defective in their responses to antigens and soluble mitogens. We asked whether or not there is a defect in the translocation of transcription factors (TF) in CD4+ T cells of aged mice. Electrophoretic mobility shift assays of three TF that regulate IL-2 gone expression, viz., Oct 1/2, NFkB, and AP-1, in nuclear extracts of cells stimulated with immobilized anti-CD3ϵ revealed no significant difference between cells of young and old mice. The nuclear levels of all three TF were lower in cells of both young and aged mice that were stimulated with Con A and lower in aged than in young. Similar assays of consensus sequences 1 and 2 (CS1 and CS2) TF involved in IL-4 gone transcription in cells of the Th2 subset revealed significant translocation of CS1 following stimulation of both young and aged cells with anti-CD3, more in cells of young than in those of aged mice. In contrast, the most evident effect of Con A stimulation was the accumulation of CS2 in nuclei of cells of aged mice. Apparently, there is no detrimental effect of senescence on the basic mechanisms of translocation of TF. The differences between stimulation with immobilized anti-CD3ϵ and Con A can be explained by the relative abundance of memory-like CD4+ T cells which accumulate with age (and are defective in Ca 2+ mobilization and signaling) and by the poor ability of memory-like cells in the aged to respond to CD28 costimulation.