IN-SITU IMMUNE-RESPONSE IN GUT-ASSOCIATED LYMPHOID-TISSUE (GALT) FOLLOWING ORAL ANTIGEN IN TCR-TRANSGENIC MICE

Oral administration of Ag results in systemic hyporesponsiveness terme d oral tolerance. The regulatory cells induced by oral Ag are effectiv e in the suppression of Th1-type autoimmune diseases. We examined the cytokine microenvironment in gut-associated lymphoid tissue in respons e to orally administered OVA in OVA TCR-transgenic mice. Mice were fed a low (0.5 mg) or high (500 mg) dose of OVA one time or five times. I mmunohistochemical analysis demonstrated increased IL-4, IL-10, and TG F-beta in the gut within 6 h of a low-dose feeding and after five low- dose or high dose feedings. IFN-gamma and IL-2 either decreased or sho wed no change, with the exception of a small transient increase in IL- 2 at 6 h after a low dose. Increases in IL-4 and IL-10 were found in t he dome of the Peyer's patch, and increases in TGF-beta were observed in the interfollicular region and the villi, IL-10 was also substantia lly increased in the villi, IL-4 and IL-10 were produced predominately by CD4(+) T cells. TGF-beta was found predominately in macrophages an d CD4(+) T cells. Peyer's patches had a marked up-regulation of TGF-be ta mRNA as measured by RT-PCR, These results demonstrate the different ial activation of cytokine production in discrete regions of gut-assoc iated lymphoid tissue. The induction of cytokines known to inhibit aut oimmune disease at the site of Ag absorption indicates an important ro le for the mucosal immune system in the establishment of oral toleranc e.