Mechanisms of tolerance induced by TGF beta-treated APC: CD4 regulatory T cells prevent the induction of the immune response possibly through a mechanism involving TGF beta

Eur J Immunol. 2004 Apr;34(4):1021-30. doi: 10.1002/eji.200324547.


Transforming growth factor beta (TGF beta)-treated antigen-presenting cells (APC) pulsed with antigen induce tolerance in mice, i.e. inhibition of IFN-gamma production and delayed type hypersensitivity response. Although evidence suggests that regulatory T cells are involved, their mechanism of action is currently unknown and is the subject of the present study. Both CD4 and CD8 splenic T cells from mice injected i.v. with adherent thioglycolate-elicited peritoneal exudate cells cultured with TGF beta(2) and antigen (TGF beta-treated APC) transferred tolerance to naive recipients. Interestingly, TGF beta-treated APC from class II knockout mice were unable to induce tolerance in wild-type mice, whereas wild-type TGF beta-treated APC could induce tolerance in CD8 knockout mice. TGF beta was detected in cultures of lymphoid cells from mice injected with TGF beta-treated APC, and treatment with anti-TGF beta antibody in vivo impaired tolerance induction. TGF beta appeared to be involved in both the development of CD4 regulatory T cells and the effector function of the CD4 regulatory T cells. In summary, the important findings in this study are that CD4, and not CD8, regulatory T cells are required for tolerance induced by TGF beta-treated APC in naive mice, and tolerance appears to be mediated by a mechanism involving TGF beta.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adoptive Transfer
  • Animals
  • Antigen-Presenting Cells
  • CD4-Positive T-Lymphocytes / immunology*
  • Female
  • Immune Tolerance*
  • Mice
  • Mice, Knockout
  • Thioglycolates / immunology
  • Transforming Growth Factor beta / immunology*


  • Thioglycolates
  • Transforming Growth Factor beta