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.
P-Selectin and P-Selectin Glycoprotein Ligand 1 Are Major Determinants for Th1 Cell Recruitment to Nonlymphoid Effector Sites in the Intestinal Lamina Propria
W. Haddad and C.J. Cooper contributed equally to this work.
The online version of this article includes supplemental material.
Abbreviations used in this paper: APC, allophycocyanin; C2GlcNAcT-I, core 2 β−1,6-N-acetylglucosaminyl transferase I; Fuc-T VII, fucosyltransferase VII; LP, lamina propria; MAdCAM, mucosal addressin cell adhesion molecule; MLN, mesenteric LN; PLN, peripheral LN; PP, Peyer's patches; PSGL-1, P-selectin glycoprotein ligand 1.
Wael Haddad, Cristine J. Cooper, Zheng Zhang, Jeffrey B. Brown, Yuechun Zhu, Andrew Issekutz, Ivan Fuss, Hae-ock Lee, Geoffrey S. Kansas, Terrence A. Barrett; P-Selectin and P-Selectin Glycoprotein Ligand 1 Are Major Determinants for Th1 Cell Recruitment to Nonlymphoid Effector Sites in the Intestinal Lamina Propria . J Exp Med 4 August 2003; 198 (3): 369–377. doi: https://doi.org/10.1084/jem.20020691
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