1. Antigen-induced regulatory T cells
by Stephane Vigouroux, Eric Yvon, Ettore Biagi, and Malcolm K. Brenner
Blood
Volume 104(1):26-33
July 1, 2004
©2004 by American Society of Hematology

2. The induction of antigen-specific regulatory T cells.
The induction of antigen-specific regulatory T cells. The following 3 strategies can be distinguished. (A) Antigen presentation by dendritic cells (DCs) especially dedicated to the induction of regulatory T cells (Trs; mucosal or cutaneous DCs or plasmacytoid DCs). The molecular mechanisms underlying the tolerogenic properties of these DCs remain to be elucidated. (B) Antigen presentation by antigen-presenting cells (APCs) with suboptimal costimulation, achieved through use of CD3, CD4, CD8, or CD40-ligand monoclonal blocking antibodies or immature APCs. (C) Antigen presentation by mature APCs with an additional regulatory signal provided by either cell-surface molecules such as LFA-3, ICOS-ligand, Notch-ligand, or soluble factors, such as IL10 with or without TGFβ, α-MSH (melanocyte-stimulating hormone), or high doses of antithrombin III.
Stephane Vigouroux et al. Blood 2004;104:26-33
©2004 by American Society of Hematology

3. Antigen-induced regulatory T cells: cellular basis of the antigen specificity.
Antigen-induced regulatory T cells: cellular basis of the antigen specificity. (A) Antigen specificity is ensured at 3 stages: presentation, activation, and recognition. (i) Presentation. A dendritic cell (DC) is presented to a conventional T cell (T) combined with a regulatory signal provided by, or accompanying the DC. The regulatory signal induces differentiation of the antigen-specific conventional T cell into an antigen-specific regulatory T cell (Tr). (ii) Activation. The Tr must encounter the same antigen again in order to become activated and fully competent to suppress the specific immune response. This antigen-driven activation ensures that suppression is limited to a particular target. (iii) Recognition. Two mechanisms support the antigen-specificity target cell (APC or T cell) recognition by Trs. First, some Trs specifically recognize MHC class I antigens on allogeneic APCs. The second mechanism is illustrated in Figure 2B. (B) Antigen-specific recognition of CD8 effector T cells by regulatory T cells. This mechanism has been described in a murine model of skin allotransplantation.30 The Trs acquire allogeneic MHC class I molecules from APCs and express them on their surface. This transfer allows the Trs to recognize autologous cytotoxic CD8 effector T cells bearing a TCR specific for the transferred MHC class I molecule.
Stephane Vigouroux et al. Blood 2004;104:26-33
©2004 by American Society of Hematology

4. Antigen-induced regulatory T cells: 3 mechanisms of suppression.
Antigen-induced regulatory T cells: 3 mechanisms of suppression. (A) After antigen-specific recognition of the target DCs, Trs inhibit CD40, CD80, and CD86 up-regulation. (B) After recognition of its specific antigen, Tr secretes IL10 and/or TGFβ. (C) Tr activates the FAS–FAS ligand cytolytic pathway to kill the effector target T cell (T) after its specific recognition.
Stephane Vigouroux et al. Blood 2004;104:26-33
©2004 by American Society of Hematology