Functional Changes of T-Cell Subsets with Age and CMV Infection.

Fakhri Hassouneh,Diana Van Heemst,Graham Pawelec,P Eline Slagboom,David Goldeck,Rafael Solana,Alejandra Pera

doi:10.3390/ijms22189973

Abstract

Cytomegalovirus (CMV) latent infection and aging contribute to alterations in the function and phenotype of the T-cell pool. We have demonstrated that CMV-seropositivity is associated with the expansion of polyfunctional CD57+ T-cells in young and middle-aged individuals in response to different stimuli. Here, we expand our results on the effects of age and CMV infection on T-cell functionality in a cohort of healthy middle-aged and older individuals stratified by CMV serostatus. Specifically, we studied the polyfunctional responses (degranulation, IFN-γ and TNF-α production) of CD4+, CD8+, CD8+CD56+ (NKT-like), and CD4−CD8− (DN) T-cells according to CD57 expression in response to Staphylococcal Enterotoxin B (SEB). Our results show that CD57 expression by T-cells is not only a hallmark of CMV infection in young individuals but also at older ages. CD57+ T-cells are more polyfunctional than CD57− T-cells regardless of age. CMV-seronegative individuals have no or a very low percentages of cytotoxic CD4+ T-cells (CD1017a+) and CD4+CD57+ T-cells, supporting the notion that the expansion of these T-cells only occurs in the context of CMV infection. There was a functional shift in T-cells associated with CMV seropositivity, except in the NKT-like subset. Here, we show that the effect of CMV infection and age differ among T-cell subsets and that CMV is the major driving force for the expansion of highly polyfunctional CD57+ T-cells, emphasizing the necessity of considering CMV serology in any study of immunosenescence.

Highlights

IntroductionOn aging, the immune system undergoes profound changes, loosely termed immunosenescence, that can affect the outcome of the immune response [3]
polyfunctional indices (PI) was evaluated among the four groups (Middle-aged CMV-seropositive, Middle-aged CMVseronegative, Old CMV-seropositive, and Old CMV-seronegative) to assess the effect of age and CMV infection on T-cell responses to Staphylococcal Enterotoxin B (SEB)
Our results show that in middle-aged and older overtly healthy individuals, the main factor driving the expansion of CD57+ T-cells is CMV infection

Summary

Introduction

On aging, the immune system undergoes profound changes, loosely termed immunosenescence, that can affect the outcome of the immune response [3] The impact of these age-related changes on the immune system has been associated clinically with decreased efficacy of vaccines, an increase in the frequency and severity of infectious diseases, and an increased incidence of chronic inflammatory disorders [3,4]. These alterations are associated with phenotypical and functional changes affecting a variety of immune cells, especially T-cells [5,6]. Recent epidemics of emerging pathogens that have a differential immune response depending on age, such as SARS-CoV-2, illustrate the crucial importance to understand the basis of an adequate response to new antigens and the relevance of factors such as age or CMV infection

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Results

Conclusion