Human TSLP directly enhances expansion of CD8+ T cells
Human TSLP directly enhances expansion of CD8+ T cells
复制标题
DOI：
10.1111/j.1365-2249.2008.03731.x
复制
发表时间：
2008-10-01
影响因子：
4.6
通讯作者：
Chiba, T.
中科院分区：
文献类型：
--
作者：
Akamatsu, T.;Watanabe, N.;Chiba, T.
人胸腺基质淋巴细胞生成素（TSLP）通过直接或间接激活树突状细胞（DC）促进CD4（+）T细胞增殖。尽管TSLP激活的DC诱导CD8（+）T细胞增殖，但TSLP是否直接作用于CD8（+）T细胞尚不清楚。在这项研究中，我们发现，T细胞受体刺激激活的人CD8（+）T细胞表达TSLP受体（TSLPR），TSLP直接增强活化的CD8（+）T细胞的增殖。尽管来自外周血的未刺激的人CD8（+）T细胞不表达TSLPR，但由抗CD3加抗CD28激活的CD8（+）T细胞表达TSLPR。在T细胞受体刺激后，TSLP直接增强活化的CD8（+）T细胞的扩增。有趣的是，使用巨细胞病毒（CMV）特异性pp65肽脉冲的单核细胞来源的DC，我们发现，尽管白细胞介素2允许CMV特异性和非特异性CD8（+）T细胞扩增，但TSLP仅诱导CMV特异性CD8（+）T细胞扩增。这些结果表明，人TSLP直接增强CD8（+）T细胞的扩增，TSLP对靶抗原特异性CD8（+）T细胞扩增的直接和间接作用可能有利于过继细胞转移免疫治疗。
Human thymic stromal lymphopoietin (TSLP) promotes CD4(+) T-cell proliferation both directly and indirectly through dendritic cell (DC) activation. Although human TSLP-activated DCs induce CD8(+) T-cell proliferation, it is not clear whether TSLP acts directly on CD8(+) T cells. In this study, we show that human CD8(+) T cells activated by T-cell receptor stimulation expressed TSLP receptor (TSLPR), and that TSLP directly enhanced proliferation of activated CD8(+) T cells. Although non-stimulated human CD8(+) T cells from peripheral blood did not express TSLPR, CD8(+) T cells activated by anti-CD3 plus anti-CD28 did express TSLPR. After T-cell receptor stimulation, TSLP directly enhanced the expansion of activated CD8(+) T cells. Interestingly, using monocyte-derived DCs pulsed with a cytomegalovirus (CMV)-specific pp65 peptide, we found that although interleukin-2 allowed expansion of both CMV-specific and non-specific CD8(+) T cells, TSLP induced expansion of only CMV-specific CD8(+) T cells. These results suggest that human TSLP directly enhances expansion of CD8(+) T cells and that the direct and indirect action of TSLP on expansion of target antigen-specific CD8(+) T cells may be beneficial to adoptive cell transfer immunotherapy.