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Published online before print February 14, 2006

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© by The Society for Leukocyte Biology
Journal of Leukocyte Biology, doi:10.1189/jlb.0805474

Received for publication August 23, 2005.
Revised December 15, 2005.
Accepted for publication January 1, 2006.

Article

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

Mei-Lien Cheng ^*, Hsin-Wei Chen ^*, Jy-Ping Tsai ^*, Yi-Ping Lee ^*, Yan-Chung Shih ^*, Chung-Ming Chang , and Chou-Chik Ting ^*@

*Immunology Group and Department of Intramural Research Affairs, National Health Research Institutes, Taiwan, Republic of China

^@ To whom correspondence should be addressed. E-mail: gting{at}nhri.org.tw.

	Abstract

Recent evidence showed that transforming growth factor- (TGF-) 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- 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- but augmented by interleukin (IL)-2, whereas the CD8⁺ memory cells from TGF--pretreated MLC (MLC-TGF-) 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- reduces the CTL activity in CD8⁺ memory cells. The increase by IL-2 and the reduction by TGF- of the CTL responses were clonal-specific. TGF- 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- was restricted severely, and the restriction was clonal-specific, thus offering direct evidence to show that TGF- induces clonal restriction of CD8⁺ memory cell expansion.

Key Words: interleukin-2 • mixed lymphocyte culture • cytotoxic T lymphocyte

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