IDENTIFICATION OF HOMING RECEPTORS THAT MEDIATE THE RECRUITMENT OF CD4 T-CELLS TO THE GENITAL-TRACT FOLLOWING INTRAVAGINAL INFECTION WITH CHLAMYDIA-TRACHOMATIS
Ka. Kelly et Rg. Rank, IDENTIFICATION OF HOMING RECEPTORS THAT MEDIATE THE RECRUITMENT OF CD4 T-CELLS TO THE GENITAL-TRACT FOLLOWING INTRAVAGINAL INFECTION WITH CHLAMYDIA-TRACHOMATIS, Infection and immunity, 65(12), 1997, pp. 5198-5208
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 inv
estigated the mechanism(s) which mediates CD4 lymphocyte migration to
the genital mucosa by identifying molecules that could support this pr
ocess. me found that primarily CD4 cells were recruited to the genital
tract (GT) during primary and challenge MoPn infection. Peak levels w
ere Pound 21 days after primary inoculation (15.4% +/- 2.7%) and 7 day
s (31.3% +/- 8.5%) after challenge but diminished after resolution of
infection, The CD4 cells appeared to be recruited to the GT in respons
e to infection since these cells expressed the profile of activated, o
r memory, cells, We also observed up-regulation of homing receptors co
ntaining LFA-1 (CD11a) and alpha 4 (CD49d) on GT CD4 cells over the co
urse of infection. Furthermore, the mucosal homing receptor chain, bet
a 7, but not the peripheral homing receptor chain beta 1 (CD29), was d
etected on GT CD4 cells, MoPn-infected GT tissue expressed the endothe
lial cell Ligands vascular cell adhesion molecule 1 (VCAM-1), intracel
lular adhesion molecule 1 (ICAM-1), and mucosal vascular addressin cel
l adhesion molecule 1 (MAdCAM-1), which correspond to the homing recep
tors on GT CD4 cells. Interestingly, VCAM-1 and MAdCAM-1 were not expr
essed in the GTs of uninfected mice but were temporarily induced follo
wing infection, indicating that expression of endothelial ligands in t
he GT are regulated by chlamydial infection, These data suggest that r
ecruitment of CD4 cells to the GT is mediated through LFA-1:ICAM-1 and
alpha 4 beta 7:MAdCAM-1-VCAM-1 interactions.