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

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.

Reduced Immunosenescence of Peripheral Blood T Cells in Parkinson’s Disease with CMV Infection Background

“…In our healthy cohorts of young and elderly donors (YHD and HD), we registered an age-associated increase in the proportion of senescent CD57 + cells in accordance with the data reported previously [ 52 ]. CMV-positive individuals demonstrated higher levels of CD57 + cells in CD56 − and CD56 + T cell subsets than CMV-negative donors from YHD and HD groups ( Figure 5 a and Figure 8 a).…”

Cytomegalovirus infection reduced CD70 expression, signaling and expansion of viral specific memory CD8+ T cells in healthy human adults

“…Consequently, chronic or latent CMV infection can eventually lead to the inflation of terminally differentiated memory CD8 + T cells and immune dysfunction in old adults [6][7][8]. Recent study of CMV infection in healthy young and middleaged adults showed increased CD57 expression in T cells [9], but it is unknown whether such increase only in CMV-specific or in non CMV-specific T cells. Overall, the molecular mechanisms of CMV infection caused changes of CMV-specific CD8 + T cells in healthy young and middle-aged adults is not fully examined.…”

T‐lymphocyte subtyping: an early warning and a potential prognostic indicator of active cytomegalovirus infection in patients with sepsis

“…These studies suggest that CMV reactivation may have the potential to serve as a sepsis-related proinflammatory factor and immune activation indicator, and demonstrate that bone marrow-derived cells are activated by CMV infection and differentiated into specific functional effector cells. A recent study by Hassouneh et al 38 indicated that CMV infection leads to functional changes in T-cell subtypes. Therefore, it is reasonable to assume that CMV infection may impair cytotoxic lymphocyte response to CMV, which in turn contributes to poor Figure 3.…”

“…A recent study by Hassouneh et al . 38 indicated that CMV infection leads to functional changes in T‐cell subtypes. Therefore, it is reasonable to assume that CMV infection may impair cytotoxic lymphocyte response to CMV, which in turn contributes to poor prognosis in patients with sepsis.…”