title: Normal ageing is associated with an increase in Th2 cells, MCP-1 (CCL1) and RANTES (CCL5), with differences in sCD40L and PDGF-AA between sexes.
abstract: We have observed T helper type 2 (Th2) polarization of systemic immunity in patients with metastatic malignant melanoma. We hypothesized that similar changes in systemic immunity occur with ageing and may be permissive for the development of melanoma. We analysed the peripheral blood of 389 healthy blood donors. All subjects were profiled for peripheral blood T cell and B cell subsets, and 58 of these subjects were profiled for antigen-specific cytotoxic T cell subsets [cytomegalovirus (CMV), influenza and melanoma antigen recognized by T cells 1 (MART-1)]. Ninety-five separate healthy subjects underwent profiling of 42 plasma cytokines. Ageing was associated positively with CD4(+) CD294(+)  Th2 cells, and associated negatively with CD3(+)  T cells, cytotoxic T cells and T helper cells. Ageing was also associated negatively with CMV-, influenza- and MART-1-specific naive and CD8(+)  T cells. There were significant increases in plasma monocyte chemotactic protein 1 (MCP-1) (CCL1) and regulated upon activation normal T cell expressed and secreted (RANTES) (CCL5) with age. We observed differences in cytokine profiles between males and females; specifically, women had higher levels of sCD40L and PDGF-AA. In summary, we demonstrated in healthy blood donors that ageing was associated with an increase in cellular Th2 bias and a decline in total numbers of T cells. Additionally, there was an increase in MCP-1 and RANTES with ageing. Women had higher levels of sCD40L and PDGF-AA than men.
authors.affiliation: Departments of Oncology Medicine, Division of Hematology Immunology Biomedical Statistics and Informatics Women's Health Clinic, Division of General Internal Medicine, Mayo Clinic Rochester, MN 55905, USA.
authors.forename: A S
authors.initials: AS
authors.lastname: Mansfield
authors.forename: W K
authors.initials: WK
authors.lastname: Nevala
authors.forename: R S
authors.initials: RS
authors.lastname: Dronca
authors.forename: A A
authors.initials: AA
authors.lastname: Leontovich
authors.forename: L
authors.initials: L
authors.lastname: Shuster
authors.forename: S N
authors.initials: SN
authors.lastname: Markovic
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000276:immunology* / Q000378:metabolism; D016175:B-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism; D017252:CD3 Complex / Q000276:immunology / Q000378:metabolism; D015704:CD4 Antigens / Q000276:immunology / Q000378:metabolism; D023201:CD40 Ligand / Q000276:immunology / Q000378:metabolism*; D018932:Chemokine CCL2 / Q000276:immunology / Q000378:metabolism*; D018946:Chemokine CCL5 / Q000276:immunology / Q000378:metabolism*; D016207:Cytokines / Q000276:immunology / Q000378:metabolism; D006801:Humans; D008297:Male; D008545:Melanoma / Q000276:immunology / Q000378:metabolism; D008875:Middle Aged; D010982:Platelet-Derived Growth Factor / Q000276:immunology / Q000378:metabolism*; D011971:Receptors, Immunologic / Q000276:immunology / Q000378:metabolism; D011982:Receptors, Prostaglandin / Q000276:immunology / Q000378:metabolism; D012737:Sex Factors; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism; D018418:Th2 Cells / Q000276:immunology* / Q000378:metabolism; D055815:Young Adult
chemical_list: C111835:CCL2 protein, human; C483024:CCL5 protein, human; D017252:CD3 Complex; D015704:CD4 Antigens; D018932:Chemokine CCL2; D018946:Chemokine CCL5; D016207:Cytokines; D010982:Platelet-Derived Growth Factor; D011971:Receptors, Immunologic; D011982:Receptors, Prostaglandin; C075278:platelet-derived growth factor A; D023201:CD40 Ligand; C036293:prostaglandin D2 receptor