CD28− T cells: their role in the age-associated decline of immune function

Abstract

SummaryThe accumulation of CD28 − T cells, particularly within the CD8 subset, is one of the most prominent changes during T cell homeostasis and function associated with aging in human. CD28, a major costimulatory receptor, is responsible for the optimal antigen-mediated T cell activation, proliferation, and survival of T cells. CD28 − T cells exhibit reduced antigen receptor diversity, defective antigeninduced proliferation, and a shorter replicative lifespan while showing enhanced cytotoxicity and regulatory functions. Gene expression analyses reveal profound changes of CD28 − T cells in comparison to their CD28 + counterparts and support their functional differences. Here we review the recent advance of our understanding of CD28− T cells and their role in age-associated decline of immune function.

Regulation of NKG2D+CD8+T-cell-mediated antitumor immune surveillance: Identification of a novel CD28 activation-mediated, STAT3 phosphorylation-dependent mechanism

“…Barber et al showed in a recent study that simultaneous stimulation of TCR and the less common co-stimulatory receptor NKG2D activated b-catenin pathway with downregulated anti-inflammatory cytokines. 28 By contrast, deficiency of CD28 on CD8 C T lymphocytes leads to the loss of proliferation capacity, 29 desensitization of CD8 C T cells under stimulation, 30 increase of apoptotic potential, 31 and even impairment for CD8 C T cell effector functions. 32 The CD8 C CD28 ¡ T cell population is therefore believed to be involved in the pathogenesis of Chagas disease, 33 chronic lymphocytic leukemia, 34 CMV infection, 35 Crohn's disease, 36 EBV infection, 37 melanoma, 38 myeloma, 39 rheumatoid arthritis, 40 systemic lupus erythromatosus, 41 Wegener's granulomatosis, 42 and so on.…”

DNA methylation and healthy human aging

“…A recent study showed that patterns of DNA methylation associated with age can easily be confounded with signatures of specific white blood cell types, as the relative frequencies of white blood cells change over the lifespan (Weng et al ., 2009; Jaffe & Irizarry, 2014). For example, if the frequency of T cells declines with age, then a site that is methylated in T cells may show declining methylation when comparing across ages, but this is due to the change in cell frequency rather than at the site itself.…”

Cellular senescence impact on immune cell fate and function

“…The loss of CD28 is not only a result of T‐cell receptor (TCR) activation. Indeed, in the presence of certain cytokines (IL‐2, IL‐7, and IL‐15), type I interferon (IFN‐α and IFN‐β), and TNF‐α, the CD28 loss is accelerated (for review, see Weng et al ., 2009). CD28 loss occurs more rapidly among CD8 T cells relative to their CD4 counterparts, presumably due to a faster turnover in the CD8 compartment.…”