Loss of Intra-Epithelial Endocervical Gamma Delta (GD) 1 T Cells in HIV-Infected Women

Abstract

Problem Human gamma delta (GD) T cells play a well-documented role in epithelial barrier surveillance and protection. Two subsets of GD T cells, defined by the use of either the Vdelta2 (GD2) or Vdelta1 (GD1) TCR, predominate. We hypothesized that endocervical GD T cells play important role in lower genital tract anti-HIV immune responses. Method of Study HIV infected (n=18) and HIV uninfected (n=19) pre-menopausal women participating in the WIHS cohort were recruited. Frequency and phenotype of GD T cells were determined in endocervical cytobrush samples and peripheral blood by multicolor flow cytometry. Results We found depletion of GD2 cells in the blood of HIV infected women as well as significant decrease in the frequency of endocervical GD1 cells compared to uninfected women. Conclusions We report for the first time, the GD1 cells are a predominant endocervical T cell subset that is significantly decreased in HIV infected women.

Mucosal and Systemic γδ+ T Cells Associated with Control of Simian Immunodeficiency Virus Infection

“…While we observed no depletion of Vδ2 T cells in SIV-infected macaques in comparison to the naïve animals, this population of cells has been reported to be lost and/or to become dysfunctional early following HIV/SIV infection (6-8, 16-18). Alteration in γδ T cells subsets has been widely shown during HIV infection (5, 17, 18, 44). In contrast only a single report concerning Vδ1/Vδ2 ratio alterations in SIV infected Rhesus macaques has appeared (8), showing a marginally significant difference in blood between naïve and SIV- infected macaques.…”

“…In addition to the blood and intestinal tissue, γδ T cells are also present in uterine tissue (21) and the endocervix (17). In the FRT, the upper tract (fallopian tubes, uterus and endocervix) is lined by a single layer of columnar epithelial cells joined by tight junctions.…”

“…Increased activation and factors important for immune responses have been reported in the ectocervix/endocervix, while the endometrium has shown high expression of factors that support HIV infectivity and favor HIV replication (25). Vδ1 is the predominant γδ T cell subset in the endocervix of uninfected women, but its frequency decreases in HIV positive women, along with that of Vδ2 T cells in both the endocervix and blood (17). However, no functionality of γδ T cells in the FRT has been assessed, and in general innate and adaptive immune responses in the FRT to HIV/SIV infection have not been completely defined because of complex regulation by female sex hormones and the degree of compartmentalization (22, 23, 26 - 29).…”

γδ T‐cell responses during HIV infection and antiretroviral therapy

“…10 However, they have been observed to expand in the blood in patients with cytomegalovirus infection, CD4 T-cell deficiency and B-cell leukaemia. 29 Multiple reports have since described an inversion of the typical Vd2:Vd1 T-cell ratio in the peripheral blood of HIV-infected/AIDS patients, [30][31][32][33] which was quickly determined to represent an increase in Vd1 T-cell frequency 30,[32][33][34][35][36][37][38][39][40][41][42][43][44] and a depletion of Vd2Vc9 T cells. In 2017, an estimated 36.9 million people were currently infected with the virus of which 1.8 million were children under the age of 15.…”

“…[11][12][13][14][15] HIV-1 (herein referred to as HIV) infection still remains one of the most challenging health issues worldwide. [31][32][33]35,38,[41][42][43][44][45][46][47][48] Subsequent investigations have focused on the mechanisms behind this expansion/depletion, as well as the relationship of cd T subsets to HIV disease progression. Despite increasing awareness of the disease and improved access to antiretroviral therapy (ART), approximately 5000 individuals become newly infected every day.…”