Subpopulations of equine blood lymphocytes expressing regulatory T cell markers
Subpopulations of equine blood lymphocytes expressing regulatory T cell markers
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DOI：
10.1016/j.vetimm.2010.11.020
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发表时间：
2011-03-15
影响因子：
1.8
通讯作者：
de Mestre, Amanda M.
中科院分区：
文献类型：
--
作者：
Robbin, Melissa G.;Wagner, Bettina;de Mestre, Amanda M.
在许多哺乳动物物种中，已经描述了几个具有免疫调节活性的不同T淋巴细胞亚群。本研究对18匹6个月至23岁的马外周血中表达调节性T细胞(Treg)标志物的细胞进行了表型分析，使用了细胞内和细胞表面标志物的抗体，包括Forkhead box P3(FOXP3)、CD4、CD8、CD25、干扰素-γ(IFN-Gamma)和白介素10(IL-10)。在外周血中，平均2.2+/-0.2%的CD4+和0.5+/-0.1%的CD8+淋巴细胞表达FOXP3。15岁及以上的马的CD4+FOXP3+细胞的平均百分比(1.5%)显著低于6岁及以下的马(2.7%)，但雌雄之间以及马与马之间没有差异。商陆刺激外周血单个核细胞可诱导CD25和FOXP3的表达，高峰分别出现在培养48h和72h。活化的CD4+FOXP3+细胞表达干扰素-γ(占FOXP3+细胞的35%)或IL-10(9%)。以CD25(-)、CD25(-)、CD25(DIM)和CD25(高)亚群进行细胞分选，以确定FOXP3的表达。分选后即刻，CD4(+)CD25(高)细胞群中的CD4+FOXP3+细胞百分比(22.7-26.3%)高于CD4(+)CD25(DIM)细胞(17%)，但在IL-2静息后的CD4(+)CD25(DIM)和CD4(+)CD25(高)细胞中的比例相似(9-14%)。在CD4(+)CD25(-)群体中，只有不到2%的细胞表达FOXP3。这些结果表明，表达与调节性T细胞相关的分子的马淋巴细胞亚群具有异质性。CD4+FOXP3+细胞可能代表自然Tregs，其中CD4+FOXP3+IL-10+细胞代表激活的自然Tregs或诱导性Tregs，而CD4+FOXP3+干扰素-γ+细胞可能代表激活的Th1细胞。2010爱思唯尔B.V.版权所有。
Several distinct T lymphocyte subpopulations with immunoregulatory activity have been described in a number of mammalian species. This study performed a phenotypic analysis of cells expressing regulatory T cell (Treg) markers in the peripheral blood of a cohort of 18 horses aged 6 months to 23 years, using antibodies to both intracellular and cell surface markers, including Forkhead box P3 (FOXP3), CD4, CD8, CD25, interferon gamma (IFN-gamma) and interleukin 10 (IL-10). In peripheral blood, a mean of 2.2 +/- 0.2% CD4+ and 0.5 +/- 0.1% CD8+ lymphocytes expressed FOXP3. The mean percentage of CD4+FOXP3+ cells was found to be significantly decreased in horses 15 years and older (1.5%) as compared to horses 6 years and younger (2.7%), but did not differ between females and males and ponies and horses. Activation of peripheral blood mononuclear cells by pokeweed mitogen resulted in induction of CD25 and FOXP3 expression by CD4+ cells, with peak expression noted after 48 and 72 h in culture respectively. Activated CD4+FOXP3+ cells expressed IFN-gamma (35% of FOXP3+ cells) or IL-10 (9% FOXP3+ cells). Cell sorting was performed to determine FOXP3 expression by CD4(+)CD25(-), CD4(+)CD25(dim) and CD4(+)CD25(high) subpopulations. Immediately following sorting, the percentage of CD4+FOXP3+ cells was higher within the CD4(+)CD25(high) population (22.7-26.3%) compared with the CD4(+)CD25(dim) (17% cells) but was similar within the CD4(+)CD25(dim) and CD4(+)CD25(high) cells after resting in IL-2 (9-14%). Fewer than 2% of cells in the CD4(+)CD25(-) population expressed FOXP3. These results demonstrate heterogeneity in equine lymphocyte subsets that express molecules associated with regulatory T cells. CD4+FOXP3+ cells are likely to represent natural Tregs, with CD4+FOXP3+IL-10+ cells representing either activated natural Tregs or inducible Tregs, and CD4+FOXP3+IFN-gamma+ cells likely to represent activated Th1 cells. 2010 Elsevier B.V. All rights reserved.