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. Author manuscript; available in PMC: 2011 Jan 1.
Published in final edited form as: Results Probl Cell Differ. 2010;51:217–235. doi: 10.1007/400_2008_13

Fig. 1. Potential Mechanisms of ECDI-fixed Ag-coupled cell (Ag-SP) Tolerance.

Fig. 1

(A) Schematic representation of Ag-SP formation. Donor cells [bulk splenocytes or red blood cells (RBCs)] are fixed with ethylene carbodiimide (ECDI) in the presence of peptide for 1 hour at 4°C to generate Ag-SP. (B–D) Possible mechanisms of Ag-SP-induced tolerance: Ag-SP can induce tolerance by direct (B) or indirect mechanisms (C, D). (B) Donor Ag-SP can directly interact with host antigen-specific T cells delivering signal 1 (MHC/peptide:TCR) without signal 2 (co-stimulation; B7-1,-2/CD28; CD40/CD40L), rendering the cells anergic. (C) Alternatively Ag-SP can induce indirect or cross-tolerance as the donor Ag-SP undergo apoptosis, leading to phagocytic uptake by host splenic antigen presenting cells (APCs), which then can present peptide fragments to host T cells inducing anergy. (D) Another possible mechanism for Ag-SP tolerance is the indirect generation/expansion of a Th2 or regulatory T cell (Treg) population, which through bystander suppression can also render antigen-specific CD4+ T cells tolerant.