Early HIV-1 infection is associated with reduced frequencies of cervical Th17 cells.

Abstract

The hallmark of HIV infection is progressive but variable rates of systemic and mucosal CD4 depletion, leading to immunodeficiency. The impact of early HIV infection on cervical CD4 T-cell populations in humans remains poorly described. We analyzed cytobrush-derived immune cells by flow cytometry and cytokines in cervicovaginal lavage from participants in early HIV (<6 months postinfection), chronic HIV, and HIV-uninfected controls. CD4:CD8 ratios declined rapidly in both the cervix and the blood following HIV infection. In contrast, absolute cervical CD4 T-cell counts in early HIV were comparable to HIV-uninfected participants, declining only in chronic infection. Early HIV infection was associated with increases in RANTES and MIP3a in cervicovaginal fluids. Concurrently, slight increases in activated cells (CD38HLA-DR) and higher levels of CTLA4 expression on Tregs in the cervix were observed. Although study groups did not differ with respect to levels of CCR5, integrin B7, or CD69, the frequencies of Th17 cells (defined as CCR6CCR10) was reduced by >10-fold in early HIV infection and Th1 cells (defined as CCR6CXCR3) were reduced by >2-fold. Although CCR6CCR10 cells did not differ in HIV receptor expression, these cells produced higher levels of interferon gamma and interleukin 17. These data support the model of initial CD4 T-cell depletion followed by overall T-cell influx in response to infection and concomitant increases in immune activation, inflammation, and regulatory markers. These data are among the earliest characterization of the cellular milieu in the female genital tract following male-to-female HIV transmission.