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.
Clin Exp Immunol. 2012 Nov;170(2):186-93. doi: 10.1111/j.1365-2249.2012.04644.x.
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.
我们观察到转移性恶性黑色素瘤患者的全身性免疫 Th2 型极化。我们假设,全身性免疫的类似变化也会随着年龄的增长而发生,并且可能允许黑色素瘤的发展。我们分析了 389 名健康献血者的外周血。所有受试者均进行外周血 T 细胞和 B 细胞亚群分析,其中 58 名受试者进行了细胞毒性 T 细胞亚群(巨细胞病毒(CMV)、流感和 T 细胞识别的黑色素瘤抗原 1(MART-1))的抗原特异性分析。95 名单独的健康受试者对 42 种血浆细胞因子进行了分析。年龄与 CD4+CD294+Th2 细胞呈正相关,与 CD3+T 细胞、细胞毒性 T 细胞和辅助性 T 细胞呈负相关。年龄也与 CMV、流感和 MART-1 特异性幼稚和 CD8+T 细胞呈负相关。随着年龄的增长,血浆单核细胞趋化蛋白 1(MCP-1)(CCL1)和激活正常 T 细胞表达和分泌(RANTES)(CCL5)显著增加。我们观察到男性和女性之间的细胞因子谱存在差异;具体而言,女性 sCD40L 和 PDGF-AA 的水平更高。总之,我们在健康献血者中证明,年龄的增长与细胞 Th2 偏倚增加和 T 细胞总数减少有关。此外,MCP-1 和 RANTES 的水平也随着年龄的增长而增加。女性 sCD40L 和 PDGF-AA 的水平高于男性。