T Lymphocytes from Tissue Non-Specific Alkaline Phosphatase Heterozygous Mice Induce a Milder Colitis in the T Cell Transfer Model of Colitis

Intestinal and tissue non-specific alkaline phosphatase (IAP and TNAP) are coexpressed in mouse colon, and the latter predominates in inflammatory conditions. T cells from TNAP +/- mice (showing a dramatic drop in TNAP expression) produce less cytokines when stimulated than those from wild type animals in vitro. We tested the hypothesis that TNAP expressed in T lymphocytes is involved in the inflammatory response in vivo. RAG-/- mice were transferred with CD4+ CD62L+ cells, enriched in naïve lymphocytes, isolated by magnetic separation from spleen cells obtained from either TNAP+/- (TNAP -/- mice die early after birth) or the control TNAP +/+ C57BL/6J mice. In this model the T cells transferred expand in the recipient mice and in the course of 4-8 weeks evoke a chronic inflammatory response in the large intestine. Our results indicate that colitis was attenuated in the animals transferred with TNAP +/- cells compared with those receiving wild type cells, based on macroscopic parameters (lower fibrosis), decreased plasma levels of IFNγ (57%) and dampened cytokine production by splenocytes ex vivo(32-40% lower TNF and 57% lower IFNg). We conclude that TNAP of T lymphocytes modulates the inflammatory response in the mouse colon.