Regulatory T cells reversibly suppress cytotoxic T cell function independent of effector differentiation

Immunity 25, 129– 141, July 2006

 Speaker: 葉恭誌                     Date: 2006/10/18 15:00~16:00

Commentator: 王崇任醫師         Place: 601教室

Abstract:

    It is now well recognized that regulatory T cells (Treg) play a central role in the control of both reactivity to self-antigens and alloimmune response, but the cellular and molecular mechanisms remain largely elusive. In vitro tissue-culture experiments have shown that Treg cells can inhibit the proliferation of effector T cells by direct cell-cell contact. However, recent in-vivo studies indicate that inhibition of CD8⁺ cytotoxic T lymphocytes (CTL) proliferation is not always necessary to achieve Treg-dependent suppression¹. The authors directly visualized how CTLs interact with target antigen-presenting cells in the presence or absence of activated Treg cells in mouse lymph nodes. First, they showed that regulatedCTLs exhibited no defect in motility, ability to form antigen-dependent conjugates with target cells. Second, they found that, although the granule content of CTLs and their expression of lytic effector molecules did not change in the presence of Treg cells, there was delayed lytic-granule release, which impaired the ability of CTLs to induce target cell death before the cell-cell conjugates dissociate. Further investigation showed that suppression of CTLs function by Treg cells was dependent on transforming growth factor-bsignaling and was reversible upon in vivo removal of Treg cells, but did not require prolonged physical interactions with Treg cells. These observations indicate that Treg cells can blunt T cell responses by selectively modulating terminal effector function of CTLs.

References:

1.      Chen, M.L. et al. Regulatory T cells suppress tumor-specific CD8+ T cell cytotoxicity through TGF-b signals in vivo. Proc. Natl. Acad. Sci. USA 102, 419-424, 2005.

2.      Mempel, T.R. et al. Regulatory T cells reversibly suppress cyotoxic T cell function independent of effector differentiation. Immunity 25, 129-141, 2006.