title: CMV latent infection improves CD8+ T response to SEB due to expansion of polyfunctional CD57+ cells in young individuals.
abstract: 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.
authors.affiliation: Department of Immunology, Maimonides Institute for Biomedical Research (IMIBIC) - Reina Sofía University Hospital - University of Cordoba, Cordoba, Spain.
authors.forename: Alejandra
authors.initials: A
authors.lastname: Pera
authors.affiliation: Department of Immunology, Maimonides Institute for Biomedical Research (IMIBIC) - Reina Sofía University Hospital - University of Cordoba, Cordoba, Spain.
authors.forename: Carmen
authors.initials: C
authors.lastname: Campos
authors.affiliation: Department of Immunology, Maimonides Institute for Biomedical Research (IMIBIC) - Reina Sofía University Hospital - University of Cordoba, Cordoba, Spain.
authors.forename: Alonso
authors.initials: A
authors.lastname: Corona
authors.affiliation: Immunology Unit, Department of Physiology, University of Extremadura, Cáceres, Spain.
authors.forename: Beatriz
authors.initials: B
authors.lastname: Sanchez-Correa
authors.affiliation: Immunology Unit, Department of Physiology, University of Extremadura, Cáceres, Spain.
authors.forename: Raquel
authors.initials: R
authors.lastname: Tarazona
authors.affiliation: Singapore Immunology Network (SIgN), Biopolis, Agency for Science, Technology and Research, Singapore, Singapore.
authors.forename: Anis
authors.initials: A
authors.lastname: Larbi
authors.affiliation: Department of Immunology, Maimonides Institute for Biomedical Research (IMIBIC) - Reina Sofía University Hospital - University of Cordoba, Cordoba, Spain.
authors.forename: Rafael
authors.initials: R
authors.lastname: Solana
mesh_terms: D000293:Adolescent; D000328:Adult; D000367:Age Factors; D017252:CD3 Complex / Q000378:metabolism; D018959:CD57 Antigens / Q000378:metabolism*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D003586:Cytomegalovirus Infections / Q000276:immunology*; D004768:Enterotoxins / Q000737:chemistry; D005260:Female; D005434:Flow Cytometry; D005786:Gene Expression Regulation; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000166:cytology; D052118:Lysosomal-Associated Membrane Protein 1 / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D055815:Young Adult
chemical_list: D017252:CD3 Complex; D018959:CD57 Antigens; D004768:Enterotoxins; D052118:Lysosomal-Associated Membrane Protein 1; D014409:Tumor Necrosis Factor-alpha; C031818:enterotoxin B, staphylococcal; D007371:Interferon-gamma