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Cytomegalovirus drives V?2neg ?? T cell inflation in many healthy virus carriers with increasing age.

ABSTRACT: Cytomegalovirus (CMV) usually causes lifelong asymptomatic infection, but over time can distort immune profiles. Recent reports describe selective expansion of V?2(neg) ?? T cells in healthy and immunocompromised CMV carriers. Having shown previously that virus-specific CD8(+) and CD4(+) T cell responses are increased significantly in elderly CMV carriers, probably driven by chronic stimulation, we hypothesized that V?2(neg) ?? T cells may also be expanded with age. Our results show that V?2(neg) ?? T cells are increased significantly in CMV-seropositive healthy individuals compared to CMV-seronegative controls in all age groups. The differences were most significant in older age groups (P?

SUBMITTER: Alejenef A

PROVIDER: S-EPMC4008987 | biostudies-literature | 2014 Jun

REPOSITORIES: biostudies-literature

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Cytomegalovirus drives Vδ2neg γδ T cell inflation in many healthy virus carriers with increasing age.

Alejenef A A Pachnio A A Halawi M M Christmas S E SE Christmas S E SE Moss P A H PA Khan N N

Clinical and experimental immunology 20140601 3

Cytomegalovirus (CMV) usually causes lifelong asymptomatic infection, but over time can distort immune profiles. Recent reports describe selective expansion of Vδ2(neg) γδ T cells in healthy and immunocompromised CMV carriers. Having shown previously that virus-specific CD8(+) and CD4(+) T cell responses are increased significantly in elderly CMV carriers, probably driven by chronic stimulation, we hypothesized that Vδ2(neg) γδ T cells may also be expanded with age. Our results show that Vδ2(neg ...[more]

PMID: 24547915

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Project description:UnlabelledAlterations in memory CD8 T cell responses may contribute to the high morbidity and mortality caused by seasonal influenza A virus (IAV) infections in older individuals. We questioned whether memory CD8 responses to this nonpersistent virus, to which recurrent exposure with new strains is common, changed over time with increasing age. Here, we show a direct correlation between increasing age and narrowing of the HLA-A2-restricted IAV V? and V? T cell repertoires specific to M1 residues 58 to 66 (M158-66), which simultaneously lead to oligoclonal expansions, including the usage of a single identical VA12-JA29 clonotype in all eight older donors. The V? repertoire of older individuals also had longer CDR3 regions with increased usage of G/A runs, whose molecular flexibility may enhance T cell receptor (TCR) promiscuity. Collectively, these results suggest that CD8 memory T cell responses to nonpersistent viruses like IAV in humans are dynamic, and with aging there is a reduced diversity but a preferential retention of T cell repertoires with features of enhanced cross-reactivity.ImportanceWith increasing age, the immune system undergoes drastic changes, and older individuals have declined resistance to infections. Vaccinations become less effective, and infection with influenza A virus in older individuals is associated with higher morbidity and mortality. Here, we questioned whether T cell responses directed against the highly conserved HLA-A2-restricted M158-66 peptide of IAV evolves with increasing age. Specifically, we postulated that CD8 T cell repertoires narrow with recurrent exposure and may thus be less efficient in response to new infections with new strains of IAV. Detailed analyses of the VA and VB TCR repertoires simultaneously showed a direct correlation between increasing age and narrowing of the TCR repertoire. Features of the TCRs indicated potentially enhanced cross-reactivity in all older donors. In summary, T cell repertoire analysis in older individuals may be useful as one of the predictors of protection after vaccination.

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Cytomegalovirus drives V?2neg ?? T cell inflation in many healthy virus carriers with increasing age.

Publications

Cytomegalovirus drives Vδ2neg γδ T cell inflation in many healthy virus carriers with increasing age.

Similar Datasets

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