Cytomegalovirus infection modulates the phenotype and functional profile of the T-cell immune response to mycobacterial antigens in older life

Article


Terrazzini, Nadi, Bajwa, Martha, Vita, Serena, Thomas, David, Smith, Helen, Vescovini, Rosanna, Sansoni, Paolo and Kern, Florian 2014. Cytomegalovirus infection modulates the phenotype and functional profile of the T-cell immune response to mycobacterial antigens in older life. Experimental Gerontology. 54, pp. 94-100.
AuthorsTerrazzini, Nadi, Bajwa, Martha, Vita, Serena, Thomas, David, Smith, Helen, Vescovini, Rosanna, Sansoni, Paolo and Kern, Florian
Abstract

Infection with Cytomegalovirus is associated with accelerated immunosenescence. Expansions of CMV-specific T cell responses have previously been demonstrated to affect the ability of T cells to respond to other infections. Most people above 60 years of age display M. tuberculosis-specific immunity because of vaccination, exposure, or both. T-cell responses can be assessed by measuring intracellular IFN-γ in vitro after tuberculin stimulation. Here we investigated tuberculin-specific CD4 T-cell responses in independently living healthy older people in the South of England using flow-cytometry. Individuals were investigated for tuberculin and CMV-specific T-cell immunity using in vitro antigen stimulation followed by intracellular staining for IFN-γ, TNF-α, IL2, as well as degranulation and CD154 upregulation. We also examined a control group of younger individuals (20–35 years of age). There was no significant difference between older and young people in regards to tuberculin responsiveness of CD4 T-cells; however, older people seemed to show more outliers. Increased responsiveness to tuberculin was significantly correlated to CMV responsiveness but not age. In older donors, the memory phenotype of tuberculin-induced T-cells was significantly skewed towards a more terminal differentiation phenotype in CMV-infected compared to uninfected individuals and the degree of skewing correlated quantitatively with the size of the CMV-specific CD4 T-cell response. This is a fundamental advance over previous reports of changes of the tuberculin-specific CD4 T-cell response with CMV serostatus. Our results show that how the immune system responds to CMV has a fundamental impact on the phenotype and function of the immune response to mycobacterial antigens in older life.

JournalExperimental Gerontology
Journal citation54, pp. 94-100
ISSN0531-5565
Year2014
Accepted author manuscript
License
CC BY
Web address (URL)http://dx.doi.org/10.1016/j.exger.2013.12.007
Publication dates
PrintJun 2014
Publication process dates
Deposited13 Mar 2015
Accepted18 Dec 2013
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