HIV infection impairs CD8+ resident memory T cell frequency in cervical mucosae

Abstract

Abstract A critical challenge in establishing a cure for HIV is the elimination of reservoirs of infection. A proposed approach is to reactivate HIV replication in infected cells and eliminate them by eliciting functional CD8+ T-cells. Due to their location and rapid and efficient response, CD8+ resident memory T cells (TRM) represent an ideal candidate, but their frequency and localization in HIV-infected subjects had not been evaluated. Therefore, we quantified frequencies of TRM cells by immunohistochemistry detection of CD8 and CD69 in cervical tissues from 5 HIV-infected and 5 non-infected women. In addition, migration assays of peripheral blood mononuclear cells (PBMC) from HIV-positive and negative donors were performed by plating one million PBMC on the top of a migration chamber placed in a well seeded with confluent HeLa cells. After 24 hours, cells that migrated to the bottom chamber were collected for flow cytometry evaluation. In cervical tissues, TRM numbers and frequencies were significantly different in basal membranes (0.93% in HIV-negative versus 0% in HIV-positive subjects, p=0.006), whereas no differences were seen for total CD8+ T cells. Moreover, in samples from HIV-positive subjects, lower frequencies of CD8+ CD69+ CD103+ T cells were detected between the cells migrated to the bottom chamber in samples from HIV-infected subjects (0.86% versus 3.54%, p=0.002, in HIV-negative versus HIV-positive). In HIV-positive donors, the frequency of CD4+ CD69+ CD103+ expressing CCR5 was significantly lower than for HIV-negative, while expression of CXCR3 and CCR7 were comparable. We propose that HIV impairs frequencies of TRM in the cervical mucosa at least in part by reducing CD8+ T cell migration through a CCR5-mediated mechanism.