Identification of preferential CD4+ T-cell targets for HIV infection in the cervix

Abstract

A better understanding of the cellular targets of HIV infection in the female genital tract may inform HIV prevention efforts. Proposed correlates of cellular susceptibility include the HIV co-receptor CCR5, peripheral homing integrins, and immune activation. We used a CCR5-tropic pseudovirus to quantify HIV entry into unstimulated endocervical CD4(+) T cells collected by cytobrush. Virus entry was threefold higher into cervix-derived CD4(+) T cells than blood, but was strongly correlated between these two compartments. Cervix-derived CD4(+) T cells expressing CD69, α(4)β(7), or α(4)β(1) were preferential HIV targets; this enhanced susceptibility was strongly correlated with increased CCR5 expression in α(4)β(7)(+) and CD69(+) CD4(+) T cells, and to a lesser extent in α(4)β(1)(+) CD4(+) T cells. Direct binding of gp140 to integrins was not observed, integrin inhibitors had no effect on virus entry, and pseudotypes with an env that preferentially binds α(4)β(7) still demonstrated enhanced entry into α(4)β(1)(+) cells. In summary, a rapid and sensitive HIV entry assay demonstrated enhanced susceptibility of activated endocervical CD4(+) T cells, and those expressing α(4)β(7) or α(4)β(1). This may relate to increased CCR5 expression by these cell subsets, but did not appear to be due to direct interaction of α(4)β(7) or α(4)β(1) with HIV envelope.

Tenofovir Inhibits Wound Healing of Epithelial Cells and Fibroblasts from the Upper and Lower Human Female Reproductive Tract

“…While some of the molecules increased by TFV in the present study possess anti-HIV activity in vitro in the micromolar range (i.e elafin and CCL20)293037, doses in the nanomolar range or lower seem to be preferentially chemotactic3839. In particular, CCL20 is chemoattractant for Th17 cells, high susceptible targets for HIV infection4041. Our results and those of others42 suggest that TFV creates a proinflammatory environment leading to the recruitment of HIV target cells at the wound site.…”

Concise Review: Wharton's Jelly: The Rich, but Enigmatic, Source of Mesenchymal Stromal Cells

“…In the latter cases, therefore, the harvested cell population may demonstrate various degrees of heterogeneity dependent upon the method employed. Conversely, the only cell isolation information provided by some authors is that “MSCs were isolated using the classical adhesion method,” 41 which clearly renders the reader incapable of knowing what cells have been employed. Furthermore, as various authors have used terms describing various regions, or zones, of Wharton's jelly differently (see above) it is rarely possible to glean from the published methods, which cells are specifically being cultured in experiments, or more importantly, employed in clinical trials (see below).…”

Tissue instruction for migration and retention of TRM cells

“…On the other hand, the α4β1 integrin is highly expressed on CD4 T RM in the vagina following TK− HSV-2 infection [9], while α1β2 integrin is expressed by lung parenchymal CD4 T cells [35]. Human cervical CD69+ CD4 T cells also express α4β1 in addition to α4β7 integrin [63]. Future studies are needed to define the integrins required to retain CD8 T RM and CD4 T RM in their respective homes.…”