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, CJ Cooper, Z Zhang, JB Brown… - The Journal of …, 2003 - rupress.org
W Haddad, CJ Cooper, Z Zhang, JB Brown, Y Zhu, A Issekutz, I Fuss, H Lee, GS Kansas…
The Journal of experimental medicine, 2003rupress.org
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 …
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.
rupress.org