Activation of Extrathymic T Cells and Granulocytes in the Liver and Intestine by Intraperitoneal Administration of Cholera Toxin

Abstract

Cholera toxin (CT) is known to be not only an intestinal inflammatory toxin but also an agent with immuno-adjuvant activity. In both cases, CT is usually administered orally. To determine the intrinsic property of CT which invades the body and its effect on the immune system, we used an intraperitoneal route for the administration of CT into mice. Although an intraperitoneal injection of CT decreased the number of thymus-derived T cells (due to apoptosis) in the thymus and systemic immune organs, it rather stimulated extrathymic T cells in the liver and intestine in terms of the number and function. This was confirmed by the phenotypic and morphologic studies. At this time, an increase in the production of both IL-4 and IFNy (i.e., Th0 type cytokine profile) was induced in sera. Moreover, granulocytes were also found to be activated at various sites in the body. Since CT induced systemic tissue damage as well as intestinal inflammation, such activated granulocytes might also be responsible for systemic inflammation. Consistent activation of extrathymic T cells in the intestine by the intraperitoneal administration of CT suggests that this route might also be associated with the induction of their immuno-adjuvant activity or intestinal inflammation.