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P-Selectin and P-Selectin Glycoprotein Ligand 1 Are Major Determinants for Th1 Cell Recruitment to Nonlymphoid Effector Sites in the Intestinal Lamina Propria

Wael Haddad¹, Cristine J. Cooper¹, Zheng Zhang², Jeffrey B. Brown¹, Yuechun Zhu¹, Andrew Issekutz⁴, Ivan Fuss⁵, Hae-ock Lee¹, Geoffrey S. Kansas³ and Terrence A. Barrett¹

¹ Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL 60611
² Department of Surgery, Northwestern University Feinberg School of Medicine, Chicago, IL 60611
³ Department of Microbiology–Immunology, Northwestern University Feinberg School of Medicine, Chicago, IL 60611
⁴ Department of Pediatrics, Pathology, and Microbiology–Immunology, Dalhousie University, Halifax, Nova Scotia, Canada, B3J 3G9
⁵ Mucosal Immunity Section, Laboratory of Clinical Investigation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892

Address correspondence to Terrence A. Barrett, Dept. of Medicine, Northwestern University Medical School, 745 N. Fairbanks, Searle 10-455, Chicago, IL 60611. Phone: (312) 503-0293; Fax: (312) 908-6192; email: tabarrett{at}northwestern.edu

The recruitment of activated T cell subsets to sites of effector immune responses is mediated by homing receptors induced upon activation in secondary lymphoid tissue. Using an adoptive transfer model, the intestinal recruitment of CD4⁺ T cells activated with intraperitoneal antigen in complete Freund's adjuvant was examined. The data demonstrate that activated CD4⁺ T cells recruited to intestinal Peyer's patches (PP) and lamina propria (LP) up-regulate functional P-selectin glycoprotein ligand 1 (PSGL-1). Blockade of IL-12 inhibited functional PSGL-1 expression and reduced PP and LP CD4⁺ T cell recruitment by >40%. P-Selectin blockade reduced LP recruitment of activated cells by 56% without affecting PP recruitment. Studies of mice examined 3 d after adoptive transfer of differentiated T cell subsets revealed that Th1 but not Th2 cells were recruited to small intestine PP and LP. Mucosal addressin cell adhesion molecule blockade reduced Th1 recruitment to PP by 90% and to LP by >72%, whereas P-selectin blockade reduced Th1 recruitment to PP by 18% and Th1 recruitment to LP by 84%. These data suggest that IL-12–induced functional PSGL-1 expression is a major determinant for the recruitment of Th1 effector cells to noninflamed as well as inflamed intestine.

Key Words: memory T cells • lamina propria • small intestine • interleukin-12 • leukocyte migration

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