Pgp‐1^hi T lymphocytes accumulate with age in mice and respond poorly to concanavalin A

Abstract

Aging is associated with an accumulation of T cells functionally hyporesponsive to the effects of mitogens such as concanavalin A. Recent studies in mice and human have identified surface markers useful for distinguishing antigen-stimulated memory T cells from virgin T cells. In mice, memory T cells within the CD8+ cell population have been shown to express relatively high levels of the cell surface glycoprotein Pgp-1. On the theory that aging might diminish the supply of virgin thymic emigrants without compromising the production of memory T cells, we examined the proportion of Pgp-1hiCD4+ and CD8+ cells in the spleen, blood and lymph nodes of mice of varying age. We found a dramatic (2.5-fold) age-associated increase in the percentage of cells with the Pgp-1hi phenotype. By limiting dilution methods, the frequency of concanavalin A-responsive T cells was found to be significantly reduced in the Pgp-1hi cell pool, whether measured by interleukin 2-dependent proliferation, interleukin 2 production or generation of cytotoxic effectors. Pgp-1hi and Pgp-1lo T cells from young mice proliferate equally well when stimulated by optimal doses of phorbol myristate acetate and ionomycin suggesting that the poor responses to concanavalin A do not simply reflect low viability. Aging leads both to an increase in mitogen-hyporesponsive Pgp-1hi T cells, and also to lower responsiveness of cells in the Pgp-1hi subset.

A high density of tertiary lymphoid structure B cells in lung tumors is associated with increased CD4+T cell receptor repertoire clonality

“…Previous reports have reinforced the concept of age-related shifts of the TCR repertoire in the peripheral compartment toward memory T cells in both mouse models and humans, with na€ ıve T cells maintained in part by homeostatic proliferation. [60][61][62] This ratio of na€ ıve to memory T cells is reduced with age, as is TCR repertoire diversity in the na€ ıve T cells, consistent with the CD4 C results shown here in the peripheral compartment, as well as more shared CD4…”

Enhanced efferocytosis by dendritic cells underlies memory T-cell expansion and susceptibility to autoimmune disease in CD300f-deficient mice

“…Such individuals also have higher levels of memory and effector T cells, 46 yet are in general hypo-responsive and referred to as immunosenescent. [47][48][49][50] Other than the higher frequency of memory and activated T cells in aged CD300f-deficient mice and the presence of elevated ANA, the T-cell proliferation in response to TCR stimulation, the activation status of macrophages or DC based on co-stimulatory molecule expression, and the levels of inflammatory or anti-inflammatory cytokines were similar between CD300f-deficient and WT mice, suggesting an immunosenescent status in aged mice. Thus, our data indicate that the autoimmune-risk status generated by CD300f deficiency occurs in the context of immunosenescence, which explains the absence of overt disease pathologies.…”

Naive T Cells Are Resistant to Anergy Induction by Anti-CD3 Antibodies

“…Several reports have indeed demonstrated that while naive T cells are optimally stimulated by soluble anti-CD3 mAbs, memory cells preferentially respond to insoluble forms of the same Ab (36,40). Similarly, other widely used T cell mitogens (including bacterial superantigens or lectins) have been shown to preferentially stimulate naive T cells, further illustrating the differences in the integration of TCR signals between T cell subsets (35,41). These observations suggest that responsiveness to anti-CD3 mAbs reflects cell differentiation rather than immunocompetence, and suggest that conventional mitogens (including lectins, bacterial superantigens, and anti-TCR complex Abs) are not suited for the evaluation of T cell competence in anergy-related studies.…”