Functional diversity of CMV-specific T-cells is maintained in older people and significantly associated with protein specificity and response size

Bajwa Joseph, Martha, Vita, Serena, Vescovini, Rosanna, Larsen, Martin, Sansoni, Paolo, Terrazzini, Nadia, Caserta, Stefano, Thomas, David, Davies, Kevin A, Smith, Helen and Kern, Florian (2016) Functional diversity of CMV-specific T-cells is maintained in older people and significantly associated with protein specificity and response size. International Journal of Infectious Diseases, 214 (9). pp. 1430-1437. ISSN 1201-9712

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Abstract

Background: Parallel up-regulation of several T-cell effector functions (‘polyfunctionality’) is believed to be critical for the protection against viruses but thought to decrease in large T-cell expansions, in particular at older ages. The factors determining T-cell polyfunctionality are incompletely understood. Here we revisit the question of CMV-specific T-cell polyfunctionality, including a wide range of T-cell target proteins, response sizes, and participant ages. Methods: Polychromatic flow-cytometry was used to analyze the functional diversity (CD107, CD154, IL-2, TNF, IFN-) of CD4 and CD8 T-cell responses to 19 CMV proteins in a large group of young and older UK participants. A group of oldest old people (>85years) was included to explore these parameters in exceptional ‘survivors’. Polyfunctionality was assessed for each proteinspecific response subset by subset and in aggregate across all proteins using the novel polyfunctionality index (PI).

Results: Polyfunctionality was not reduced in healthy older compared to young people. However, it was significantly related to target protein specificity. For each protein it increased with response size. In the oldest old overall T-cell polyfunctionality was significantly lower.

Discussion: Our results give a new perspective on T-cell polyfunctionality and raise the question if maintaining polyfunctionality of CMV-specific T-cells at older ages is necessarily beneficial.

Item Type: Article
Keywords: CMV-specific T-cells protein specificity response size
Schools and Departments: Brighton and Sussex Medical School > Brighton and Sussex Medical School
Brighton and Sussex Medical School > Clinical and Laboratory Investigation
Brighton and Sussex Medical School > Global Health and Infection
Subjects: R Medicine
R Medicine > R Medicine (General)
Depositing User: Sandy Gray
Date Deposited: 15 Aug 2016 06:55
Last Modified: 02 Aug 2017 09:34
URI: http://sro.sussex.ac.uk/id/eprint/62379

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Project NameSussex Project NumberFunderFunder Ref
The role of CMV-specific immunity in the association between CMV infection and vascular complicatioG1198DUNHILL MEDICAL TRUSTR278/0213