CMV-specific T-cell responses at older ages: broad responses with a large central memory component may be key to long-term survival

Martha Bajwa, Serena Vita, Rosanna Vescovini, M. Larsen, Paolo Sansoni, Nadia Terrazzini, Stefano Caserta, David Thomas, Kevin A. Davies, Helen Smith, Florian Kern

Research output: Contribution to journalArticle

Abstract

Cytomegalovirus (CMV) infection sometimes causes large expansions of CMV-specific T cells, particularly in older people. This is believed to undermine immunity to other pathogens and to accelerate immunosenescence. While multiple different CMV proteins are recognized, most publications on age-related T-cell expansions have focused on dominant target proteins UL83 or UL123, and the T-cell activation marker interferon-γ (IFN-γ). We were concerned that this narrow approach might have skewed our understanding of CMV-specific immunity at older ages. We have, therefore, widened the scope of analysis to include in vitro-induced T-cell responses to 19 frequently recognized CMV proteins in "young" and "older" healthy volunteers and a group of "oldest old" long-term survivors (>85 years of age). Polychromatic flow cytometry was used to analyze T-cell activation markers (CD107, CD154, interleukin-2 [IL-2], tumor necrosis factor [TNF], and IFN-γ) and memory phenotypes (CD27, CD45RA). The older group had, on average, larger T-cell responses than the young, but, interestingly, response size differences were relatively smaller when all activation markers were considered rather than IFN-γ or TNF alone. The oldest old group recognized more proteins on average than the other groups, and had even bigger T-cell responses than the older group with a significantly larger central memory CD4 T-cell component.
Original languageEnglish
Pages (from-to)1212-1220
Number of pages9
JournalJournal of Infectious Diseases
Volume215
Issue number8
DOIs
Publication statusPublished - 12 Feb 2017

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Cytomegalovirus
T-Lymphocytes
Survival
Interferons
Immunity
Proteins
Tumor Necrosis Factor-alpha
Cytomegalovirus Infections
Cellular Structures
Interleukin-2
Survivors
Publications
Healthy Volunteers
Flow Cytometry
Phenotype

Bibliographical note

This is a pre-copyedited, author-produced version of an article accepted for publication in Journal of Infectious Diseases following peer review. The version of record Martha Bajwa, Serena Vita, Rosanna Vescovini, Martin Larsen, Paolo Sansoni, Nadia Terrazzini, Stefano Caserta, David Thomas, Kevin A. Davies, Helen Smith, Florian Kern; CMV-Specific T-cell Responses at Older Ages: Broad Responses With a Large Central Memory Component May Be Key to Long-term Survival. J Infect Dis 2017; 215 (8): 1212-1220 is available online at: https://doi.org/10.1093/infdis/jix080

Cite this

Bajwa, Martha ; Vita, Serena ; Vescovini, Rosanna ; Larsen, M. ; Sansoni, Paolo ; Terrazzini, Nadia ; Caserta, Stefano ; Thomas, David ; Davies, Kevin A. ; Smith, Helen ; Kern, Florian. / CMV-specific T-cell responses at older ages: broad responses with a large central memory component may be key to long-term survival. In: Journal of Infectious Diseases. 2017 ; Vol. 215, No. 8. pp. 1212-1220.
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Bajwa, M, Vita, S, Vescovini, R, Larsen, M, Sansoni, P, Terrazzini, N, Caserta, S, Thomas, D, Davies, KA, Smith, H & Kern, F 2017, 'CMV-specific T-cell responses at older ages: broad responses with a large central memory component may be key to long-term survival', Journal of Infectious Diseases, vol. 215, no. 8, pp. 1212-1220. https://doi.org/10.1093/infdis/jix080

CMV-specific T-cell responses at older ages: broad responses with a large central memory component may be key to long-term survival. / Bajwa, Martha; Vita, Serena; Vescovini, Rosanna; Larsen, M.; Sansoni, Paolo; Terrazzini, Nadia; Caserta, Stefano; Thomas, David; Davies, Kevin A.; Smith, Helen; Kern, Florian.

In: Journal of Infectious Diseases, Vol. 215, No. 8, 12.02.2017, p. 1212-1220.

Research output: Contribution to journalArticle

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T1 - CMV-specific T-cell responses at older ages: broad responses with a large central memory component may be key to long-term survival

AU - Bajwa, Martha

AU - Vita, Serena

AU - Vescovini, Rosanna

AU - Larsen, M.

AU - Sansoni, Paolo

AU - Terrazzini, Nadia

AU - Caserta, Stefano

AU - Thomas, David

AU - Davies, Kevin A.

AU - Smith, Helen

AU - Kern, Florian

N1 - This is a pre-copyedited, author-produced version of an article accepted for publication in Journal of Infectious Diseases following peer review. The version of record Martha Bajwa, Serena Vita, Rosanna Vescovini, Martin Larsen, Paolo Sansoni, Nadia Terrazzini, Stefano Caserta, David Thomas, Kevin A. Davies, Helen Smith, Florian Kern; CMV-Specific T-cell Responses at Older Ages: Broad Responses With a Large Central Memory Component May Be Key to Long-term Survival. J Infect Dis 2017; 215 (8): 1212-1220 is available online at: https://doi.org/10.1093/infdis/jix080

PY - 2017/2/12

Y1 - 2017/2/12

N2 - Cytomegalovirus (CMV) infection sometimes causes large expansions of CMV-specific T cells, particularly in older people. This is believed to undermine immunity to other pathogens and to accelerate immunosenescence. While multiple different CMV proteins are recognized, most publications on age-related T-cell expansions have focused on dominant target proteins UL83 or UL123, and the T-cell activation marker interferon-γ (IFN-γ). We were concerned that this narrow approach might have skewed our understanding of CMV-specific immunity at older ages. We have, therefore, widened the scope of analysis to include in vitro-induced T-cell responses to 19 frequently recognized CMV proteins in "young" and "older" healthy volunteers and a group of "oldest old" long-term survivors (>85 years of age). Polychromatic flow cytometry was used to analyze T-cell activation markers (CD107, CD154, interleukin-2 [IL-2], tumor necrosis factor [TNF], and IFN-γ) and memory phenotypes (CD27, CD45RA). The older group had, on average, larger T-cell responses than the young, but, interestingly, response size differences were relatively smaller when all activation markers were considered rather than IFN-γ or TNF alone. The oldest old group recognized more proteins on average than the other groups, and had even bigger T-cell responses than the older group with a significantly larger central memory CD4 T-cell component.

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