Phenotype and susceptibility to HIV infection of CD4+ Th17 cells in the human female reproductive tract.
Prevention of sexual acquisition of HIV in women requires a substantial increase in our knowledge about HIV-target cell availability and regulation in the female reproductive tract (FRT). In this study, we analyzed the phenotype and susceptibility to HIV infection of CD4(+) T cell in the endometrium (EM), endocervix (END), and ectocervix (ECT) of the FRT. We found that T helper type 17 (Th17) cells represent a major subset in FRT tissues analyzed and that Th17 cells were the main CD4(+) T-cell population expressing C-C motif chemokine receptor 5 (CCR5) and CD90. In premenopausal women, CD4(+) T cells and Th17 cells, in particular, were significantly lower in EM relative to END and ECT. Th17 cells were elevated in EM from postmenopausal women relative to premenopausal tissues but not changed in END and ECT. Susceptibility of CD4(+) T cells to HIV infection measured as intracellular p24 was lowest in the EM and highest in the ECT. Additionally, we found that Th17 cells co-expressing CCR5 and CD90 were the most susceptible to HIV infection. Our results provide valuable information for designing preventive strategies directed at targeting highly susceptible target cells in the FRT.
Department of Physiology and Neurobiology, Geisel School of Medicine at Dartmouth, Lebanon, New Hampshire, USA.
M
M
Rodriguez-Garcia
Department of Physiology and Neurobiology, Geisel School of Medicine at Dartmouth, Lebanon, New Hampshire, USA.
F D
FD
Barr
Department of Physiology and Neurobiology, Geisel School of Medicine at Dartmouth, Lebanon, New Hampshire, USA.
S G
SG
Crist
Department of Physiology and Neurobiology, Geisel School of Medicine at Dartmouth, Lebanon, New Hampshire, USA.
J V
JV
Fahey
Department of Physiology and Neurobiology, Geisel School of Medicine at Dartmouth, Lebanon, New Hampshire, USA.
C R
CR
Wira
D000328:Adult; D000368:Aged; D002584:Cervix Uteri / Q000276:immunology* / Q000473:pathology; D004198:Disease Susceptibility / Q000276:immunology / Q000473:pathology; D004717:Endometrium / Q000276:immunology* / Q000473:pathology; D005260:Female; D005786:Gene Expression Regulation / Q000276:immunology; D015658:HIV Infections / Q000276:immunology* / Q000473:pathology; D006801:Humans; D008875:Middle Aged; D017698:Postmenopause / Q000276:immunology*; D019713:Receptors, CCR5 / Q000276:immunology; D058504:Th17 Cells / Q000276:immunology* / Q000473:pathology; D018800:Thy-1 Antigens / Q000276:immunology
C584933:CCR5 protein, human; D019713:Receptors, CCR5; D018800:Thy-1 Antigens