Differential homing mechanisms regulate regionalized effector CD8αβ ⁺ T cell accumulation within the small intestine

Abstract

The CC chemokine receptor (CCR)9 is expressed on the majority of small intestinal, but few colonic, T cells, whereas its ligand CCL25 is constitutively expressed by small intestinal epithelial cells. As such, CCR9/CCL25 have been proposed to play a central role in regulating small intestinal but not colonic immune responses and thus to organize regionalized immunity within the intestinal mucosa. Here, we demonstrate that CCL25 is expressed at reduced levels by epithelial cells in the distal compared with proximal small intestine, which correlated with less efficient CCR9-dependent effector CD8␣␤ ؉ T cell entry into the ileal epithelium. In vitro-generated ␣4␤7 ؉ effector CD8␣␤ ؉ T cell entry into the lamina propria was less dependent on CCR9 than entry into the epithelium along the entire length of the small intestine and in particular in the ileum. CCR9-independent ␣4␤7 ؉ effector CD8␣␤ ؉ T cell entry was pertussis toxin-sensitive, suggesting a role for additional G␣ I-linked G protein-coupled receptors. Finally, in vivo-primed effector CD8␣␤ ؉ T cells displayed regionalized differences in their entry to the small intestinal epithelium with enhanced CCR9-independent entry to the ileum. These results highlight a hitherto underappreciated compartmentalization of immune responses within the small intestine and have direct implications for targeting strategies aimed at regulating T cell localization to the small intestinal mucosa.chemokine receptor ͉ intestinal mucosa

CCR2 Receptor Is Essential to Activate Microbicidal Mechanisms to Control Toxoplasma gondii Infection in the Central Nervous System

“…35 In vivoprimed effector CD8␣␤ ϩ T cells displayed regionalized differences in their entry to the small intestine epithelium with enhanced CCR9-independent entry to the ileum. 36 CCR1, CCR2, CCR5, and CXCR3 are increased in Toxoplasma-infected ileum, and in particular, CCR5 expression was markedly increased in Toxoplasma-primed CD8 ϩ intraepithelial T lymphocytes. 8 Our results demonstrate that despite the absence of CCR2, other chemokine receptors are involved in CD8 ϩ T lymphocyte migrations to the small intestine.…”

Enhanced differentiation of intraepithelial lymphocytes in the intestine of polymeric immunoglobulin receptor‐deficient mice

“…19 We therefore examined the expression of CCR9 on SI-IELs and CCL25 mRNA through the intestinal tract. The expression patterns of the CCR9 molecule on the SI-IELs from pIgR +/+ mice and pIgR À/À mice were similar, and CCL25 mRNA expression in the intestine was not different between these mice (see Supplementary material, Fig.…”

Anti-CD3 preconditioning separates GVL from GVHD via modulating host dendritic cell and donor T-cell migration in recipients conditioned with TBI

“…37,41 mRNA was quantified by real-time quantitative PCR using Applied Biosystems 7300 Fast Real-Time PCR System (Applied Biosystems, Forest City, CA). The primers for chemokines were previously described in the following publications: Ccl3-5, 42 Ccl17, 43 Ccl22, 43 Ccl25, 44 Ccl27, 45 Ccl28, 45 and Cxcl9-11. 37 Relative expression levels of genes were normalized within each sample to the housekeeping gene GAPDH (glyceraldehyde 3-phosphate dehydrogenase) and were presented relative to the expression in recipients of syngeneic transplants, in which BALB/c recipients that had been irradiated were injected with 5 ϫ 10 6 syngeneic TCD-BM cells as previous described.…”