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The blood of healthy individuals exhibits CD8 T cells with a highly altered TCR Vb repertoire but with an unmodified phenotype.

ABSTRACT: CD8 T cell clonal expansions (TCE) have been observed in elderly, healthy individuals as well in old mice, and have been associated with the ageing process. Both chronic latent and non-persistent viral infections have been proposed to drive the development of distinct non-functional and functional TCE respectively. Biases in TCR V? repertoire diversity are also recurrently observed in patients that have undergone strong immune challenge, and are preferentially observed in the CD8 compartment. Healthy adults can also exhibit CD8 T cells with strong alterations of their CDR3 length distribution. Surprisingly, no specific investigations have been conducted to analyze the CD8 T cell repertoire in normal adults, to determine if such alterations in TCR V? repertoire share the features of TCE. In this study, we characterized the phenotype and function of the CD8 population in healthy individuals of 25-52 years of age. All but one of the EBV-positive HLA-B8 healthy volunteers that were studied were CMV-negative. Using a specific unsupervised statistical method, we identified V? families with altered CDR3 length distribution and increased TCR V?/HPRT transcript ratios in all individuals tested. The increase in TCR V?/HPRT transcript ratio was more frequently associated with an increase in the percentage of the corresponding V?(+) T cells than with an absence of modification of their percentage. However, in contrast with the previously described TCE, these CD8(+) T cells were not preferentially found in the memory CD8 subset, they exhibited normal effector functions (cytokine secretion and cytotoxic molecule expression) and they were not reactive to a pool of EBV/CMV/Flu virus peptides. Taken together, the combined analysis of transcripts and proteins of the TCR V? repertoire led to the identification of different types of CD8(+) T cell clone expansion or contraction in healthy individuals, a situation that appears more complex than previously described in aged individuals.

SUBMITTER: Degauque N

PROVIDER: S-EPMC3124488 | biostudies-literature | 2011

REPOSITORIES: biostudies-literature

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The blood of healthy individuals exhibits CD8 T cells with a highly altered TCR Vb repertoire but with an unmodified phenotype.

Degauque Nicolas N Boeffard Françoise F Foucher Yohann Y Ballet Caroline C Brouard Sophie S Soulillou Jean-Paul JP

PloS one 20110627 6

CD8 T cell clonal expansions (TCE) have been observed in elderly, healthy individuals as well in old mice, and have been associated with the ageing process. Both chronic latent and non-persistent viral infections have been proposed to drive the development of distinct non-functional and functional TCE respectively. Biases in TCR Vβ repertoire diversity are also recurrently observed in patients that have undergone strong immune challenge, and are preferentially observed in the CD8 compartment. He ...[more]

PMID: 21738624

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Project description:A broad T cell receptor (TCR-) repertoire is required for an effective immune response. TCR-repertoire diversity declines with age. End-stage renal disease (ESRD) patients have a prematurely aged T cell system which is associated with defective T cell-mediated immunity. Recently, we showed that ESRD may significantly skew the TCR V?-repertoire. Here, we assessed the impact of ESRD on the TCR V?-repertoire within different T cell subsets using a multiparameter flow-cytometry-based assay, controlling for effects of aging and CMV latency. Percentages of 24 different TCR V?-families were tested in circulating naive and memory T cell subsets of 10 ESRD patients and 10 age- and CMV-serostatus-matched healthy individuals (HI). The Gini-index, a parameter used in economics to describe the distribution of income, was calculated to determine the extent of skewing at the subset level taking into account frequencies of all 24 TCR V?-families. In addition, using HI as reference population, the differential impact of ESRD was assessed on clonal expansion at the level of an individual TCR V?-family. CD8+, but not CD4+, T cell differentiation was associated with higher Gini-TCR indices. Gini-TCR indices were already significantly higher for different CD8+ memory T cell subsets of younger ESRD patients compared to their age-matched HI. ESRD induced expansions of not one TCR V?-family in particular and expansions were predominantly observed within the CD8+ T cell compartment. All ESRD patients had expanded TCR V?-families within total CD8+ T cells and the median (IQ range) number of expanded TCR V?-families/patient amounted to 2 (1-4). Interestingly, ESRD also induced clonal expansions of TCR V?-families within naive CD8+ T cells as 8 out of 10 patients had expanded TCR V?-families. The median (IQ range) number of expanded families/patient amounted to 1 (1-1) within naive CD8+ T cells. In conclusion, loss of renal function skews the TCR V?-repertoire already in younger patients by inducing expansions of different TCR V?-families within the various T cell subsets, primarily affecting the CD8+ T cell compartment. This skewed TCR V?-repertoire may be associated with a less broad and diverse T cell-mediated immunity.

Dataset Information

The blood of healthy individuals exhibits CD8 T cells with a highly altered TCR Vb repertoire but with an unmodified phenotype.

Publications

The blood of healthy individuals exhibits CD8 T cells with a highly altered TCR Vb repertoire but with an unmodified phenotype.

Similar Datasets

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