Clonal restriction of the expansion of antigen-specific CD8+ memory T cells by transforming growth factor-β

被引:5
|
作者
Cheng, Mei-Lien
Chen, Hsin-Wei
Tsai, Jy-Ping
Lee, Yi-Ping
Shih, Yan-Chung
Chang, Chung-Ming
Ting, Chou-Chik
机构
[1] Natl Hlth Res Inst, Dept Intramural Res Affairs, Zhunan 350, Miaoli, Taiwan
[2] Natl Hlth Res Inst, Immunol Grp, Zhunan 350, Miaoli, Taiwan
关键词
flow cytometry; mixed lymphocyte culture; cytotoxic T lymphocyte;
D O I
10.1189/jlb.0805474
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Recent evidence showed that transforming growth factor-P (TGF-beta) regulates the global expansion of CD8(+) T cells, which are CD44(hi), a marker for memory cells. However, it is not clear whether this regulatory mechanism also applies to the antigen-specific CD8(+) memory cells. By using a murine mixed lymphocyte culture (MLC) model, we examined the effect of TGF-beta on antigen-specific CD8(+) memory cells [cytotoxic T lymphocyte (CTL)]. We found that the secondary CTL response in CD8(+) memory cells from untreated MLC was not affected by TGF-beta but augmented by interleukin (IL)-2, whereas the CD8(+) memory cells from TGF-beta-pretreated MLC (MLC-TGF-beta) failed to mount a significant, secondary CTL response, even when IL-2 was added. In exploring this dichotomy, in combination with flow cytometry analysis, we found that prolonged exposure to TGF-beta reduces the CTL activity in CD8(+) memory cells. The increase by IL-2 and the reduction by TGF-beta of the CTL responses were clonal-specific;c. TGF-beta did not affect the CTL response to a third-party antigen or polyclonal T cell activation. Experiments performed with transgenic 2C cells gave similar results. Cell-cycle study performed with adoptive transfer of the cell tracker-labeled MLC cells revealed that the in vivo expansion of CD8(+) memory cells from MLC-TGF-beta was restricted severely, and the restriction was clonal-specific, thus offering direct evidence to show that TGF-beta induces clonal restriction of CD8(+) memory cell expansion.
引用
收藏
页码:1033 / 1042
页数:10
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