Age‐related changes in lymphokine production related to a decreased number of CD45RB^hi CD4⁺ T cells

Abstract

The ability of CD4+ T cells from CBA/Rij mice to produce interleukin (IL) 2 after stimulation with anti-CD3, concanavalin A, or the combination of phorbol 12-myristate 13-acetate and ionomycin declines during aging. This phenomenon was accompanied by an increased production of IL 4 and interferon-gamma. These age-related changes in lymphokine production correlated with the decrease in the percentage of CD45RBhi CD4+ T cells from about 80% in 2-month-old to about 40% in 27-month-old mice. This phenotypic shift was responsible for the decline in IL 2 production, because in young and in old mice CD45RBhi CD4+ T cells were more potent IL 2 producers than CD45RBlo cells. Moreover, old CD45RBhi CD4+ T cells produced less IL 2 than their young counterparts. Proliferative responses by T cells from old mice were lower than those of young mice, regardless whether the cultures were supplemented with IL 2, IL 4 or both lymphokines. As far as CD4+ T cells were concerned, this hyporesponsiveness was found in the CD45RBlo as well as in the CD45RBhi CD4+ T cell population.

Aging-related Deficiency of CD28 Expression in CD4+ T Cells Is Associated with the Loss of Gene-specific Nuclear Factor Binding Activity

“…2,3 Similar observations have also been reported for transformed CD4ϩCD28 null T cells without apparent genomic lesions of CD28 itself (27). Therefore, we evaluated the hypothesis that CD28 deficiency in human CD4ϩ T cells is associated with a transcriptional block.…”

“…2,3 By standard reverse transcription-PCR techniques, none of the splice variants of CD28 mRNA (27,28) were detectable. To test the hypothesis that a transcriptional block might account for the deficiency in CD28 expression, studies were initiated to isolate the 5Ј-UTR of the gene for functional assays.…”

“…Because of thymic involution from the onset of reproductive maturity, aging leads to the inability to generate new T cells. Thus, there is a progressive replacement of naive (CD45RAϩ) T cells with those having a memory (CD45ROϩ, CD29 hi , and CD44 hi ) phenotype (2)(3)(4)(5). Paradoxically, expansion of the memory T cell population is not associated with enhanced memory immune responses in the elderly.…”

Cytolytic activity of mitogen activated old and young mouse spleen cells against tumor target cells expressing high or low levels of Fas antigen

“…These include T-cell proliferation in response to stimulation through T cell receptor and co-stimulators (Engwerda et al, 1994;Lerner et al, 1988;Song et al, 1993), production and response to growth promoting cytokines (Ernst et al, 1993;Nagelkerken et al, 1991;Saxena et al, 1988) and generation of cytotoxic T-cells (Hirano and Nordin, 1976;Powers and Belshe, 1993;Mbawuike et al, 1997). We have previously characterized mitogen induced cytotoxic spleen cells from young and old mice and reported differences in their cytolytic activities (Saxena et al, 1981(Saxena et al, , 1988a.…”

Aging and CD8+ T cell immunity to respiratory virus infections

“…However, comparatively little is known about the impact of age on established memory T cells pools. Here we discuss age-related changes in memory CD8 + T cell pools elicited by influenza and parainfluenza viruses and the impact of these changes on immunity in general.A large number of studies have documented that increasing age is associated with a progressive decline in the capacity to mount effective immune responses (Burns et al, 1993;Cook et al, 1987;Effros, 2003;Grubeck-Loebenstein and Wick, 2002;Linton and Dorshkind, 2004;McElhaney, 2003;McElhaney, 2005;Miller, 1991;Miller, 1996;Murasko and Jiang, 2005;Nagelkerken et al, 1991;Phair et al, 1978;Wick et al, 2000;Zheng et al, 1997). Aged individuals typically have an impaired capacity to clear infections and also exhibit significant defects in graft rejection, delayed type hypersensitivity, and tumor rejection (Haynes and Eaton, 2005;Miller, 1996;Po et al, 2002).…”