Antigen-independent changes in naive CD4 T cells with aging.

Abstract

SummaryIn the elderly, a dramatic shift within the CD4 + T cell population occurs, with an increased proportion having a memory phenotype with markedly decreased responsiveness. To determine what aspects of the aged phenotype are dependent upon repeated contact with antigen in the environment, we examined CD4 + cells isolated from TC1L Tg n'nce. There is good evidence that no cross-reacting antigens for the Tg TCIL recognizing pigeon cytochrome c are found in the environment of the animal, so that alterations in the Tg CD4 + cells with aging are likely to be due to antigen-independent processes. We found that in aged animals, TC1L transgeneP °' CD4 + cells, although decreased in number and antigen responsiveness, maintain a naive phenotype rather than acquinng a prototypxcal aged memory phenotype. In contrast, the population of transgene 1 .... g CD4 + cells increase m proportion and express the aged phenotype. Consistent with their naive status, transgeneP °s cells of aged individuals remain CD44 l° CD45RB h~, secrete IL-2 and not IL-4 or IFN-3, upon antigenic stimulation, and require costimulation to prohferate to anti-CD3 stimulation. These findings suggest that the aging-associated shift to CD4 cells expressing the memory phenotype is dependent on antigenic stimulation. However, the decrease in antigen responsiveness of naive transgene p°~ cells, as revealed by a lower secretion of IL-2 and IL-3 and a lower proliferative capacity, suggests that additional intrinsic changes occur with aging that do not depend on encounter with antigen.

Age-Dependent Impairment of Angiogenesis

“…T-cell proliferation in vitro and in vivo declines with age in both mice and humans, and there is a shift away from naive CD4ϩ cells toward a relative increase in memory subsets. 32 The fact that we observed fewer T cells in the ischemic tissues of older mice despite similar peripheral T-cell counts in old and young mice is consistent with the notion of an age-dependent defect in transendothelial migration of T lymphocytes 33 into the target ischemic tissues. Although the precise mechanisms responsible for T-cell migration remain enigmatic, recent reports suggest that a combination of signals is required to trigger the migratory T-cell phenotype 34 and that CD4ϩ activated T cells are more likely to transmigrate than CD4Ϫ cells.…”

IFN-α Exerts Opposing Effects on Activation-Induced and IL-7–Induced Proliferation of T Cells That May Impair Homeostatic Maintenance of CD4+ T Cell Numbers in Treated HIV Infection

“…It is well established that the function of the immune system declines with age (34,35). Diminished responses to mitotic stimuli, such as IL-2, have been observed in aging people and associated with reduced receptor signaling (36). A similar mechanism involving age-related defects in CD127 (IL-7R) signaling may affect IL-7 responsiveness.…”

CD4 T–cell memory can persist in the absence of class II

“…Thus when re-stimulated, memory cells will expand rather than undergo apoptosis. mitomycin C. Few traces of the APC population are detectable in these cultures after one to two days (Zhang et al 1995) (Linton et al 1996). Thus we consider the chance of antigen stimulation in adoptive hosts to be minimal.…”