Zhang Xiaoyu, Dong Haidong, Lin Wei, Voss Stephen, Hinkley Lucinda, Westergren Melissa, Tian Guoliang, Berry Daniel, Lewellen David, Vile Richard G, Chen Lieping, Farber Donna L, Strome Scott E
Department of Otorhinolaryngology-Head and Neck Surgery, University of Maryland School of Medicine, Baltimore, MD 21201-1619, USA.
J Immunol. 2006 Nov 15;177(10):6730-7. doi: 10.4049/jimmunol.177.10.6730.
The role of human bone marrow (BM) CD8+ T cells in the immune response to viral Ags is poorly defined. We report here the identification and characterization of a functionally enhanced effector memory CD8+ T cell population (TEM) in the BM of patients undergoing total joint replacement for osteoarthritis. These BM-derived TEM differ strikingly from correlate cells in peripheral blood (PB), expressing elevated levels of CD27, HLA-DR, CD38, CD69, and unique patterns of chemokine receptors. Interestingly, while BM TEM have low levels of resting perforin and granzyme B, these molecules evidence profound up-regulation in response to TCR stimulation resulting in enhanced cytotoxic potential. Moreover, compared with the TEM subset in PB, BM CD8+ TEM cells demonstrate a more vigorous recall response to pooled viral Ags. Our results reveal that human BM serves as a repository for viral Ag-specific TEM with great therapeutic potential in vaccine development.
人类骨髓(BM)CD8 + T细胞在针对病毒抗原的免疫反应中的作用尚不清楚。我们在此报告了对因骨关节炎接受全关节置换术患者骨髓中功能增强的效应记忆CD8 + T细胞群体(TEM)的鉴定和特征。这些源自骨髓的TEM与外周血(PB)中的相关细胞显著不同,表达升高水平的CD27、HLA-DR、CD38、CD69以及趋化因子受体的独特模式。有趣的是,虽然骨髓TEM的静息穿孔素和颗粒酶B水平较低,但这些分子在TCR刺激后表现出显著上调,导致细胞毒性潜力增强。此外,与外周血中的TEM亚群相比,骨髓CD8 + TEM细胞对汇集的病毒抗原表现出更强烈的回忆反应。我们的结果表明,人类骨髓是病毒抗原特异性TEM的储存库,在疫苗开发中具有巨大的治疗潜力。