Identification of homing receptors that mediate the recruitment of CD4 T cells to the genital tract following intravaginal infection with Chlamydia trachomatis.
Murine genital infection induced with the mouse pneumonitis biovar of Chlamydia trachomatis (MoPn) elicits a short-lived protective immunity mediated primarily by Th1 CD4 cells. To understand the development of local cell-mediated immunity against C. trachomatis infection, we investigated the mechanism(s) which mediates CD4 lymphocyte migration to the genital mucosa by identifying molecules that could support this process. We found that primarily CD4 cells were recruited to the genital tract (GT) during primary and challenge MoPn infection. Peak levels were found 21 days after primary inoculation (15.4% +/- 2.7%) and 7 days (31.3% +/- 8.5%) after challenge but diminished after resolution of infection. The CD4 cells appeared to be recruited to the GT in response to infection since these cells expressed the profile of activated, or memory, cells. We also observed up-regulation of homing receptors containing LFA-1 (CD11a) and alpha4 (CD49d) on GT CD4 cells over the course of infection. Furthermore, the mucosal homing receptor chain, beta7, but not the peripheral homing receptor chain beta1 (CD29), was detected on GT CD4 cells. MoPn-infected GT tissue expressed the endothelial cell ligands vascular cell adhesion molecule 1 (VCAM-1), intracellular adhesion molecule 1 (ICAM-1), and mucosal vascular addressin cell adhesion molecule 1 (MAdCAM-1), which correspond to the homing receptors on GT CD4 cells. Interestingly, VCAM-1 and MAdCAM-1 were not expressed in the GTs of uninfected mice but were temporarily induced following infection, indicating that expression of endothelial ligands in the GT are regulated by chlamydial infection. These data suggest that recruitment of CD4 cells to the GT is mediated through LFA-1:ICAM-1 and alpha4beta7:MAdCAM-1-VCAM-1 interactions.
Kelly
K A
KA
Department of Microbiology and Immunology, University of Arkansas for Medical Sciences, Little Rock 72205, USA. kellykathleena@exchange.uams.edu
Rank
R G
RG
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D002465:Cell Movement / Q000276:immunology; D002690:Chlamydia Infections / Q000276:immunology*; D002692:Chlamydia trachomatis; D005260:Female; D005836:Genitalia, Female / Q000276:immunology* / Q000382:microbiology*; D018799:Intercellular Adhesion Molecule-1 / Q000276:immunology; D008213:Lymphocyte Activation; D051379:Mice; D008807:Mice, Inbred BALB C; D016201:Receptors, Lymphocyte Homing / Q000276:immunology*; D019010:Vascular Cell Adhesion Molecule-1 / Q000276:immunology
D016201:Receptors, Lymphocyte Homing; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1