CD117+CD44+ Stem T Cells Develop in the Thymus and Potently Suppress T-cell Proliferation by Modulating the CTLA-4 Pathway

CD117+CD44+ 干细胞在胸腺中发育,并通过调节 CTLA-4 通路有效抑制 T 细胞增殖

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作者:Yang Wei, Zhansheng Hu, Wen Gu, Gang Liu, Bingyin Shi, Enqi Liu, Tie Liu

Background

CD117 is expressed on double-negative (DN; CD4-CD8-) cells (Nat Rev Immunol 14:529-545; 2014), but whether it is expressed in other stages and its subsequent functions are unclear. We used an improved method of flow cytometry to analyze different populations of thymocytes (Sci Rep 4:5781; 2014). The expression of CD117 and CTLA-4 were directly assayed in the early stage of thymocytes.

Conclusion

These results suggest that CD44+CD117+ T cells are stem cells and a specific T-cell phenotype that initially develops in the thymus, but they do not progress through DN3 and DN4 stages, lack a DP stage, and potently suppress T-cell proliferation and modulate the CTLA-4 pathway.

Methods

Flow cytometry was used to analyze different populations of thymocytes, and T-cell proliferation assays, RT-PCR, and real-time RT-PCR were used to characterize the stem cells and examine the function of CD44+CD117+ cells.

Results

In DN cells, CD117 expression was greatest on CD44+CD25+ cells (DN2), followed by CD44+CD25- (DN1), CD44-CD25+ (DN3), and CD44-CD25- (DN4) cells. In thymocytes, CD117 expression was highest in DN cells, followed by single-positive (SP; CD4 or CD8) and double-positive (DP; CD4+CD8+) cells. Especially, CD117 expression was positively associated with CD44 and CTLA-4 expression. CTLA-4 expression was highest in DN cells, followed by SP and DP cells. CTLA-4 expression was positively associated with CD25, CD44, and Foxp3 expression. CD44+CD117+ T cells expressed more CTLA-4, which suppressed T-cell proliferation and blocked CTLA-4 to cause antibody-induced T-cell proliferation.

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