P-selectin and P-selectin glycoprotein ligand 1 are major determinants for Th1 cell recruitment to nonlymphoid effector sites in the intestinal lamina propria.
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.
Haddad
Wael
W
Dept. of Medicine, Northwestern University Medical School, 745 N. Fairbanks, Searle 10-455, Chicago, IL 60611, USA.
Cooper
Cristine J
CJ
Zhang
Zheng
Z
Brown
Jeffrey B
JB
Zhu
Yuechun
Y
Issekutz
Andrew
A
Fuss
Ivan
I
Lee
Hae-ock
HO
Kansas
Geoffrey S
GS
Barrett
Terrence A
TA
D019264:Adoptive Transfer; D000818:Animals; D002465:Cell Movement / Q000502:physiology*; D002478:Cells, Cultured; D018664:Interleukin-12 / Q000378:metabolism; D007421:Intestine, Small / Q000033:anatomy & histology / Q000276:immunology / Q000378:metabolism*; D008024:Ligands; D008213:Lymphocyte Activation; D008562:Membrane Glycoproteins / Q000276:immunology / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D019007:P-Selectin / Q000276:immunology / Q000378:metabolism*; D018417:Th1 Cells / Q000166:cytology / Q000276:immunology / Q000378:metabolism*; D018418:Th2 Cells / Q000166:cytology / Q000276:immunology / Q000378:metabolism
D008024:Ligands; D008562:Membrane Glycoproteins; D019007:P-Selectin; C084882:P-selectin ligand protein; D018664:Interleukin-12