Analyzing expression of perforin, Runx3, and thpok genes during positive selection reveals activation of CD8-differentiation programs by MHC II-signaled thymocytes

	Analyzing expression of perforin, Runx3, and thpok genes during positive selection reveals activation of CD8-differentiation programs by MHC II-signaled thymocytes
	Liu, XL; Taylor, BJ; Sun, GP; Bosselut, R
刊名	JOURNAL OF IMMUNOLOGY
	2005
卷号	175 期号:7 页码:4465-4474
通讯作者	Bosselut, R (reprint author), NCI, Lab Immune Cell Biol, NIH, Bldg 37,Room 3015, Bethesda, MD 20892 USA.,remy@helix.nih.gov
英文摘要	Intrathymic positive selection matches CD4-CD8 lineage differentiation to MHC specificity. However, it is unclear whether MHC signals induce lineage choice or simply select thymocytes of the appropriate lineage. To investigate this issue, we assessed thymocytes undergoing positive selection for expression of the CD8 lineage markers perforin and Runx3. Using both population-based and single-cell RT-PCR analyses, we found large subsets of MHC class II (MHC-II)-signaled thymocytes expressing these genes within the CD4(+)8(+) and CD4(+)8(int), but not the CD4(+)8(-) populations of signaling competent mice. This indicates that MHC-II signals normally fail to impose CD4 differentiation and further implies that the number of mature CD8 single-positive (SP) thymocytes greatly underestimates CD8 lineage choice. We next examined whether MHC-II-restricted CD4(+)8(-) thymocytes remain competent to initiate CD8 lineage gene expression. In mice in which expression of the tyrosine kinase Zap70 and thereby TCR signaling were impaired selectively in SP thymocytes, MHC-II-signaled CD4(+)8(-) thymocytes expressed perforin and Runx3 and failed to up-regulate the CD4 marker Thpok. This indicated that impairing TCR signals at the CD4 SP stage switched gene expression patterns from CD4- to CD8-lineage specific. We conclude from these findings that MHC-II-signaled thymocytes remain competent to initiate CD8-specific gene expression even after CD8 down-regulation and that CD4 lineage differentiation is not fixed before the CD4 SP stage.
学科主题	Immunology
类目[WOS]	Immunology
关键词[WOS]	CELL LINEAGE COMMITMENT ; CD8(+) T-CELLS ; TRANSCRIPTION FACTOR ; NEGATIVE SELECTION ; ANTIGEN RECEPTOR ; THYMIC SELECTION ; CD4 LINEAGE ; DIFFERENTIAL REQUIREMENTS ; STOCHASTIC MECHANISM ; TRANSGENIC MICE
收录类别	SCI
语种	英语
WOS记录号	WOS:000232092600039
内容类型	期刊论文
版本	出版稿
源URL	[http://202.127.25.143/handle/331003/1931]
专题	上海生化细胞研究所_上海生科院生化细胞研究所
推荐引用方式 GB/T 7714	Liu, XL,Taylor, BJ,Sun, GP,et al. Analyzing expression of perforin, Runx3, and thpok genes during positive selection reveals activation of CD8-differentiation programs by MHC II-signaled thymocytes[J]. JOURNAL OF IMMUNOLOGY,2005,175(7):4465-4474.
APA	Liu, XL,Taylor, BJ,Sun, GP,&Bosselut, R.(2005).Analyzing expression of perforin, Runx3, and thpok genes during positive selection reveals activation of CD8-differentiation programs by MHC II-signaled thymocytes.JOURNAL OF IMMUNOLOGY,175(7),4465-4474.
MLA	Liu, XL,et al."Analyzing expression of perforin, Runx3, and thpok genes during positive selection reveals activation of CD8-differentiation programs by MHC II-signaled thymocytes".JOURNAL OF IMMUNOLOGY 175.7(2005):4465-4474.