Maintenance of CMV-specific CD8+ T cell responses and the relationship of IL-27 to IFN-γ levels with aging

Abstract

We investigated whether healthy young (age ≤ 40) and elderly (age ≥ 65) people infected with cytomegalovirus (CMV) had similar levels of CD8+ T cell cytokine production and proliferation in response to an immunodominant CMV pp65 peptide pool given the role of CD8+ T cells in controlling viral infection and the association of CMV with immunosenescence. Plus, we determined the effects of aging and CMV-infectious status on plasma levels of IL-27, an innate immune cytokine with pro- and anti-inflammatory properties, as well as on its relationship to IFN-γ in that IL-27 can promote the production of IFN-γ. The results of our study show that young and elderly people had similar levels of CD8+ T cell proliferation, and IFN-γ and TNF-α production in response to CMV pp65 peptides. Plasma levels of IL-27 were similar between the two groups although CMV-infected young and elderly people had a trend toward increased levels of IL-27. Regardless of aging and CMV-infectious status, plasma levels of IL-27 correlated highly with plasma levels of IFN-γ. These findings suggest the maintenance of CMV pp65-specific CD8+ T cell proliferation and cytokine production with aging as well as the sustaining of circulatory IL-27 levels and its biological link to IFN-γ in young and elderly people irrespective of CMV infection.

Adjuvanted influenza-H1N1 vaccination reveals lymphoid signatures of age-dependent early responses and of clinical adverse events

“…Age is a fundamental component of experiential variation, and marked declines in adaptive responsiveness in the elderly are well known and increasingly well understood 7,27,39,40 . By contrast, age-related differences in the early (day +1) response, such as those described here, have not been widely considered.…”

Antiviral Activities of Interleukin-27: A Partner for Interferons?

“…A clinical study aligns with these data, as a positive correlation between IL-27 and IFNγ plasma levels in CMV-infected patients has been observed ( 50 ). However, contradictory findings of whether IL-27 promotes IFNγ production by T cells and NK cells have been reported.…”

“…Activation and production of IFNs and IL-27 appear connected. Clinical studies demonstrate that IL-27 and IFN levels are tightly correlated during viral infection ( 20 , 50 ). Additionally, in vitro and in vivo studies confirm that IL-27 directly induces IFN production and vice versa by various cell types, such as DCs, macrophages, NK cells, hepatocytes, and lung epithelial cells ( 18 , 20 , 28 , 29 , 36 , 39 , 40 , 43 , 44 ).…”

Development of a predictive algorithm for patient survival after traumatic injury using a five analyte blood panel

“…Despite the large age range of the trauma patients, we observed significant correlations of age with concentration of proteins including ones previously reported in the literature 21,46–55 along with several that were not significant in published data but reached significance in ours. 46,56 Age-related increases in CTACK, I-309, IL-22, IL-2ra, IL-8, IL-9, MCP-2, MIP-1a, MIP-3a, MIP-3b, and MIP-5 have not previously been described. The majority of these proteins are involved in immune cell chemotaxis with gene ontology analysis on proteins upregulated with age having 7 of 15 top enriched pathways involved chemotaxis or cell migration ( Supplemental Figure 12 ).…”