We have defined a new mode of tolerance induction resulting from continuous administration of low doses of OVA to the conjunctiva of the eye. The tolerance induced is as potent as oral tolerance and requires 50 fold less antigen. The mechanism of tolerance induction was studied using a DO11.10 TCR transgenic adoptive transfer model in which the OVA specific T cells could be monitored with the clonotypic, KJ126 mAb. Application of OVA 323-339 (25 u.g) to the conjunctiva once a day for 10 days induced rapid and sustained accumulation of KJ1-26, CD4" T cells in the draining, submandibular LN. These T cells resembled primed T cells in that they could proliferate and secrete IL-2 in vitro in response to OVA. However, upon secondary immunization of adoptive transfer mice with OVA/CFA s.c., the marked expansion of KJ1-26 cells normally seen in LN draining the site of a primary OVA/CFA immunization was inhibited in mice that received conjunctival, or i.v. OVA as a primary tolerization. Thus, T cell priming to soluble peptide or de-aggregated protein readily occurs in vivo, even in the absence of adjuvant. However, these primed cells appear to be capable of inhibiting a secondary response to OVA/CFA. It is possible that CD4 T cell priming in the absence of adjuvant induces a polarized Th2 response in vivo that is capable of down-regulating subsequent Thl responses.
|Investigative Ophthalmology and Visual Science
|Published - 1997
ASJC Scopus subject areas
- Sensory Systems
- Cellular and Molecular Neuroscience