CMV latent infection improves CD8+ T response to SEB due to expansion of polyfunctional CD57+ cells in young individuals

• Published in: PloS one Vol. 9; no. 2; p. e88538
• Main Authors: Pera, Alejandra, Campos, Carmen, Corona, Alonso, Sanchez-Correa, Beatriz, Tarazona, Raquel, Larbi, Anis, Solana, Rafael
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 12.02.2014; Public Library of Science (PLoS)
• Subjects: Adolescent; Adult; Age; Age Factors; Aging; Analysis; Antigens; Biology; Biomedical research; CD3 Complex - metabolism; CD57 antigen; CD57 Antigens - metabolism; CD8 antigen; CD8-Positive T-Lymphocytes - immunology; Cytokines; Cytomegalovirus; Cytomegalovirus infections; Cytomegalovirus Infections - immunology; Degranulation; Disease susceptibility; Enterotoxin B; Enterotoxins - chemistry; Expansion; Female; Flow Cytometry; Gene Expression Regulation; Geriatrics; HIV; Hospitals; Human immunodeficiency virus; Humans; Immune response; Immune system; Immunology; Infection; Infections; Inflammation; Influenza; Influenza vaccines; Interferon; Interferon-gamma - metabolism; Latent infection; Leukocytes, Mononuclear - cytology; Lymphocytes; Lymphocytes T; Lysosomal-Associated Membrane Protein 1 - metabolism; Male; Medical prognosis; Medicine; Middle age; Middle Aged; Older people; Physiology; Prognosis; Senescence; Staphylococcal enterotoxin B; T cell receptors; T cells; Tumor necrosis factor; Tumor Necrosis Factor-alpha - metabolism; Tumor necrosis factor-α; Vaccination; Viral infections; West Nile virus; Young Adult
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0088538

Cytomegalovirus (CMV) latent infection has a deleterious effect on the efficacy of influenza vaccination in the elderly, suggesting that CMV restricts immunological diversity impairing the immune system functionality in old age. Polyfunctional T cells produce multiple cytokines and higher amounts than mono-functional T cells. High number of polyfunctional T cells correlates with better prognosis during infection. Thus, the efficiency of T cell response associates with quality (polyfunctionality) rather than with quantity (percentage of T cells). We analyze the effect of CMV infection on CD8+ T cells polyfunctionality --degranulation (CD107a), IFN-gamma and TNF-alpha production--, from young CMV-seropositive and CMV-seronegative individuals and in middle age CMV-seropositive donors, in response to Staphylococcal Enterotoxin B (SEB). Our results show a higher percentage of polyfunctional CD8+ T cells in young CMV-seropositive individuals compared to CMV-seronegative. Also, we find an expansion of CD8+CD57+ T cells in CMV-seropositive individuals, which are more polyfunctional than CD8+CD57- cells. In middle age individuals there is a higher frequency of SEB-responding CD8+ T cells, mainly TNF-alpha or TNF-alpha/IFN-gamma producers, whereas the percentage of polyfunctional cells (IFN-gamma/TNF-alpha/CD107a) is similar to the percentages found in young CMV-seropositive. Therefore, whereas it has been shown that CMV latent infection can be detrimental for immune response in old individuals, our results indicate that CMV-seropositivity is associated to higher levels of polyfunctional CD8+ T cells in young and middle age donors. This increase in polyfunctionality, which can provide an immunological advantage in the response to other pathogens, is due to a CD8+CD57+ T cell expansion in CMV-seropositive individuals and it is independent of age. Conversely, age could contribute to the inflammation found in old individuals by increasing the percentage of cells producing pro-inflammatory cytokines. These findings highlight the necessity of further studies on the benefits/detrimental effects of CMV infection in the response to vaccination and other infections.