Naïve and memory CD8 T cell pool homeostasis in advanced aging: impact of age and of antigen-specific responses to cytomegalovirus

Abstract

Alterations in the circulating CD8+ T cell pool, with a loss of naïve and accumulation of effector/effector memory cells, are pronounced in older adults. However, homeostatic forces that dictate such changes remain incompletely understood. This observational cross-sectional study explored the basis for variability of CD8+ T cell number and composition of its main subsets: naïve, central memory and effector memory T cells, in 131 cytomegalovirus (CMV) seropositive subjects aged over 60 years. We found great heterogeneity of CD8+ T cell numbers, which was mainly due to variability of the CD8 + CD28− T cell subset regardless of age. Analysis, by multiple regression, of distinct factors revealed that age was a predictor for the loss in absolute number of naïve T cells, but was not associated with changes in central or effector memory CD8+ T cell subsets. By contrast, the size of CD8+ T cells specific to pp65 and IE-1 antigens of CMV, predicted CD28 − CD8+ T cell, antigen-experienced CD8+ T cell, and even total CD8+ T cell numbers, but not naïve CD8+ T cell loss. These results indicate a clear dichotomy between the homeostasis of naïve and antigen-experienced subsets of CD8+ T cells which are independently affected, in human later life, by age and antigen-specific responses to CMV, respectively.Electronic supplementary materialThe online version of this article (doi:10.1007/s11357-013-9594-z) contains supplementary material, which is available to authorized users.

Immunological profiling of patients with ulcerative colitis leads to identification of two inflammatory conditions and CD1a as a disease marker

“…S2). This observation is in agreement with previous data which also showed a decline of naïve T-cells and accumulation of antigen-experienced T-cells [40]. Thus, the age effect might affect observations obtained from analyzing T-cells.…”

“…Age and duration of disease resulted in decreased frequencies of naïve CD8+ and increase of frequencies of central memory CD8+ T-cells. This observation is in agreement with previous results, which also described a loss of naïve T-cells and an accumulation of experienced T- cells with age [40]. Thus, age might diminish the effect of the disease on these cell types.…”

Effects of aging on human leukocytes (part II): immunophenotyping of adaptive immune B and T cell subsets

“…CMV-specific CD8 + T cells are increased in old individuals (65-101 years), but not in middle-aged/elderly (41-64 years) individuals, based on staining with HLA-A2 CMV pp65 pentamers (Pita-Lopez et al 2009). Another report demonstrated similar levels of EBV-and CMV-specific CD8 + T cells between young (young 20-61) and old (75-82 years) individuals, identified through HLA-A2 tetramers to EBV BMLF1 and CMV pp65 epitopes, respectively (Colonna-Romano et al 2007;Vescovini et al 2014). …”

“…Similarly, spectratyping of the TCRVB genes revealed the expansion of particular segments (Pennesi et al 2001). Life-long exposure to pathogens results in an agedependent increase in antigen-experienced T cells (Vescovini et al 2014). Particularly, chronic infections, such as CMV and EBV, induce the age-dependent expansion of memory cells (Stowe et al 2007), further decreasing the T cell receptor repertoire size, making the aging immune system vulnerable to infections.…”

Narrowing of Human Influenza A Virus-Specific T Cell Receptor α and β Repertoires with Increasing Age

“…In addition, those naive T cells were identified to be more memory like, further enhancing the decline in naive T cell diversity (32). Simultaneously, as a result of accumulated exposures to many environmental antigens with age, the memory T cell pool is significantly increased and is also the subject of continuous individualized changes (33).…”