ACAID Requires iC3b during the Early Phase of Antigen and APC Contact

Abstract

Abstract: : Purpose: We have previously shown that the presence of iC3b is critical for the induction of ocular tolerance (i.e. ACAID). The present study was undertaken to determine the importance of iC3b at the time of antigen – antigen-presenting cell (APC) contact. Methods: To determine the importance of iC3b during antigen contact and processing by APCs we studied the "in vivo" model of ACAID induced by the iv injection of APC pulsed in vitro with soluble antigen in the presence of immunosuppressive factors present in the eye. In this model OVA (the antigen) and PEC (the APC) were cultured with or without purified polymeric iC3b (piC3b) for the first 12 hours. These OVA-PEC (5x10⁴) were injected intravenously into naïve Lewis rats and OVA specific DTH was measured by the foot-pad swelling assay. Results: Suppression (p< 0.05) of DTH was observed in the animals (n=6) that received an iv injection of OVA-PEC cultured with iC3b for only the first 12 hours compared to the animals (n=6) that received OVA-PEC cultured in the absence of iC3b for the first 12 hours. Conclusions: Our results provide evidence that the presence of a complement activation product –iC3b- during the early phase (within 12 hours) of antigen and APC contact is essential for the development of systemic tolerance associated with ACAID.

Keywords: ACAID • immunomodulation/immunoregulation • immune tolerance/privilege