International Immunology, Vol. 15, No. 8, pp. 945-953,
August 2003
© 2003 Japanese Society for Immunology
Deletion, but not anergy, is involved in TGF-ß-treated antigen-presenting cell-induced tolerance
1 University of Louisville Health Sciences Center, 319 Abraham Flexner Way, Louisville, KY 40202, USA
Correspondence to: M. M. Kosiewicz; E-mail: mmkosi01{at}gwise.louisville.edu
Transmitting editor: P. S. Ohashi
Intravenous injection of transforming growth factor (TGF-)-ß-treated antigen-presenting cells (APC) pulsed with antigen induces antigen-specific tolerance in both naive and previously primed mice. Although TGF-ß-treated APC-induced tolerance is associated with induction of regulatory T cells and impaired delayed-type hypersensitivity (DTH) responses, the specific mechanisms that mediate this tolerance are not currently known. The goal of the present report was to study the mechanisms involved in TGF-ß-treated APC-induced tolerance by determining the fate of the antigen-specific effector T cells that are regulated. Using a well-characterized system that allows tracking of small numbers of TCR transgenic T cells, we have found that antigen-specific T cell expansion, either in vivo or in vitro, is inhibited in mice that have been injected with TGF-ß-treated APC. The failure of antigen-specific effector T cells to expand did not appear to be due to the induction of anergy, since carboxyfluorescein diacetate succinimidyl ester (CFSE)-labeled cells divided normally in response to antigen and adjuvant in vivo, and addition of exogenous IL-2 was unable to restore T cell expansion in in vitro assays. Interestingly, the percentage of CFSE-labeled cells was decreased after >7–8 divisions following culture in vitro, which correlated with a significant increase in cell death. Cell death was prevented and the ability to expand in vitro was restored by treatment with anti-Fas ligand (FasL) antibody. In conclusion, tolerance induced by TGF-ß-treated APC appears to be associated with deletion of antigen-specific T cells involving the Fas–FasL pathway.
Keywords: anergy, Fas ligand, T cell, tolerance, transforming growth factor-ß
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  M. M. Kosiewicz, P. Alard, S. Liang, and S. L Clark Mechanisms of tolerance induced by transforming growth factor-{beta}-treated antigen-presenting cells: CD8 regulatory T cells inhibit the effector phase of the immune response in primed mice through a mechanism involving Fas ligand Int. Immunol., May 1, 2004; 16(5): 697 - 706. [Abstract] [Full Text] [PDF]
|
|