Background & aims: Oral tolerance is recognized as a central immunoregulatory phenomenon. The mechanisms of its induction remain unclear, and the role of the intestinal epithelial cells that are able to present antigens to T lymphocytes is poorly understood. In this report, we analyze under in vivo conditions the intracellular targeting of mucosally administered ovalbumin (OVA) to major histocompatibility complex (MHC) class II antigen containing compartments of enterocytes and compare these pathways between BALB/c and SCID mice, the latter being unable to generate a transferable tolerogenic moiety after a feed of OVA.
Methods: OVA, lysosome-associated membrane proteins (LAMP-1), and MHC class II antigens were localized in jejunal biopsy specimens of BALB/c and SCID mice at 0, 5, 10, 20, 40, 60, and 120 minutes after a single feed with OVA by fluorescence and electron microscopy.
Results: Ten minutes after oral administration, OVA was transported to the proximity of MHC class II antigens within LAMP-1-positive vacuoles and to the basolateral membrane of enterocytes from BALB/c strain mice. However, in SCID mice, OVA reached the paracellular spaces during the same time period through LAMP-1-negative vacuoles of enterocytes, which lacked MHC class II antigens.
Conclusions: Orally administered OVA is rapidly targeted to late endosomes containing LAMP-1 and MHC class II antigens in enterocytes of BALB/c mice but not in SCID mice bred on a BALB/c background. We suggest that this targeting process within the enterocytes is one of the requirements for the induction of oral tolerance.