Clonal restriction of the expansion of antigen-specific CD8+ memory T cells by transforming growth factor-{beta}.
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.
Immunology Group, National Health Research Institutes, Taiwan, ROC.
Mei-Lien
ML
Cheng
Hsin-Wei
HW
Chen
Jy-Ping
JP
Tsai
Yi-Ping
YP
Lee
Yan-Chung
YC
Shih
Chung-Ming
CM
Chang
Chou-Chik
CC
Ting
D000818:Animals; D000954:Antigens, Surface / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D049109:Cell Proliferation / Q000187:drug effects*; D002478:Cells, Cultured; D017635:Clonal Anergy / Q000276:immunology; D002999:Clone Cells / Q000187:drug effects / Q000276:immunology; D018920:Coculture Techniques; D015536:Down-Regulation / Q000187:drug effects / Q000276:immunology; D000939:Epitopes / Q000187:drug effects / Q000276:immunology*; D005260:Female; D005434:Flow Cytometry; D007111:Immunity, Cellular / Q000187:drug effects / Q000276:immunology; D007156:Immunologic Memory / Q000187:drug effects / Q000276:immunology*; D007376:Interleukin-2 / Q000276:immunology / Q000494:pharmacology; D007959:Lymphocyte Culture Test, Mixed; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D013602:T-Lymphocytes, Cytotoxic / Q000187:drug effects / Q000276:immunology; D016212:Transforming Growth Factor beta / Q000276:immunology* / Q000494:pharmacology
D000954:Antigens, Surface; D000939:Epitopes; D007376:Interleukin-2; D016212:Transforming Growth Factor beta