DISTINCT HOMING PATHWAYS DIRECT T-LYMPHOCYTES TO THE GENITAL AND INTESTINAL MUCOSAE IN CHLAMYDIA-INFECTED MICE

Immunity to genital tract infection with Chlamydia trachomatis is medi ated by type 1 CD4(+) T lymphocytes, To define the signals that govern lymphocyte trafficking to the genital mucosa, integrins expressed by infiltrating T cells and endothelial addressins displayed on local vas culature were characterized during the course of infection, All T cell s expressed the alpha(L) beta(2) heterodimer that binds vascular ICAM- 1, and most displayed enhanced levels of the alpha(4) beta(1) integrin that interacts with VCAM-1, alpha(E) and beta(7)(low) integrin chains were detected on approximately 15 and 30% of infiltrating T cells, re spectively, Lymphocytes derived from the spleen or draining lymph node s expressed this same integrin profile, suggesting that cells are recr uited to the genital mucosa from the systemic circulation without sign ificant selection pressure for these markers, Immunofluorescent staini ng for the corresponding vascular addressins revealed intense expressi on of VCAM-1 on small vessels within Chlamydia-infected genital tracts and up-regulation of ICAM-1 on endothelial, stromal, and epithelial c ells, Mucosal addressin cell adhesion molecule-1 was not detected with in genital tissues, These results indicate that T lymphocyte homing to the genital mucosa requires the interaction of alpha(L) beta(2) and a lpha(4) beta(1) with endothelial ICAM-1 and VCAM-1, respectively, whic h is the same pathway that directs lymphocytes to systemic sites of in flammation, Homing pathways defined for the intestinal mucosa and assu med to be relevant to all mucosal sites are not well represented in th e genital tract, The identification of T lymphocyte trafficking pathwa ys shared between systemic and mucosal tissues should facilitate vacci ne strategies aimed at maximizing immune responses against Chlamydia a nd other pathogens of the urogenital tract.