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EnglishSubversion of the CD8+ T cell pool, with a loss of naïve and accumulation of effector/effector memory cells, is a dominant aspect of T-cell immunosenescence especially in the elderly with prior Cytomegalovirus (CMV) infection. We explored the basis for variability of CD8+ T cell number and composition of its main subsets including naïve, central memory and effector memory T cells, in a cohort of CMV-seropositive subjects aged over 60 years, according to age and magnitude of anti-CMV CD8+ T cells. We observed great individual variability of CD8+ T cell number, which was mainly due to variation of CD8+CD28- T cells regardless of age. We then evaluated the relationship between magnitude of CD8+ T cell subsets, age, and anti-CMV responses quantified by both static assays against immunodominant epitopes of pp65 protein, and intracellular IFNgamma-producing functional assay against pp65 and IE-1 proteins. Analysis, by multiple regression, of independent contribution of age and anti-CMV CD8+ T cell responses to CD8+ T cell subsets variability, showed that increasing age was a predictor for absolute number of naive, but was not associated with changes in central or effector/effector memory CD8+ T cells. By contrast, magnitude of anti-CMV responses was not a predictor for naive CD8+ T cells, but strongly predicted numbers of antigen-experienced CD8+ T cells. These results indicate a clear dichotomy between age and CD8+ T cell response to CMV as independent factors subverting respectively the naive and antigen-experienced CD8+ T cell pool in later life.
| Titolo: | Variability of CD8+ T Cells Subversion According to Age and Antigen-specific Responses to Cytomegalovirus in Later Life. |
| Autori: | |
| Data di pubblicazione: | 2012 |
| Abstract: | Subversion of the CD8+ T cell pool, with a loss of naïve and accumulation of effector/effector memory cells, is a dominant aspect of T-cell immunosenescence especially in the elderly with prior Cytomegalovirus (CMV) infection. We explored the basis for variability of CD8+ T cell number and composition of its main subsets including naïve, central memory and effector memory T cells, in a cohort of CMV-seropositive subjects aged over 60 years, according to age and magnitude of anti-CMV CD8+ T cells. We observed great individual variability of CD8+ T cell number, which was mainly due to variation of CD8+CD28- T cells regardless of age. We then evaluated the relationship between magnitude of CD8+ T cell subsets, age, and anti-CMV responses quantified by both static assays against immunodominant epitopes of pp65 protein, and intracellular IFNgamma-producing functional assay against pp65 and IE-1 proteins. Analysis, by multiple regression, of independent contribution of age and anti-CMV CD8+ T cell responses to CD8+ T cell subsets variability, showed that increasing age was a predictor for absolute number of naive, but was not associated with changes in central or effector/effector memory CD8+ T cells. By contrast, magnitude of anti-CMV responses was not a predictor for naive CD8+ T cells, but strongly predicted numbers of antigen-experienced CD8+ T cells. These results indicate a clear dichotomy between age and CD8+ T cell response to CMV as independent factors subverting respectively the naive and antigen-experienced CD8+ T cell pool in later life. |
| Handle: | http://hdl.handle.net/11381/2428652 |
| Appare nelle tipologie: | 4.1b Atto convegno Volume |
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