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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-{beta}

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

*Immunology Group and {dagger}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.


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Abstract

Recent evidence showed that transforming growth factor-{beta} (TGF-{beta}) regulates the global expansion of CD8+ T cells, which are CD44hi, 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. 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.

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




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