Frequency and phenotype of Immune cell subsets in different regions of the human cervix : implications for HIV susceptibility.
Year: 2018
Type: dissertation
Abstract: Background: Although mucosal sites such as the gut have been extensively studied, less is known about the immune cell composition of the human female genital tract, a surface through which HIV is transmitted.This study aimed to determine the frequency of immune cell subsets in endocervical and ectocervical tissue sections of HIV uninfected women.Methods: Six cervical explant tissue samples were obtained from women undergoing elective hysterectomies in Prince Mshiyeni Memorial Hospital and King Edward VII Hospital, Durban, South Africa.The tissues were dissected into 2mm blocks and mechanically digested and dissociated using the mouse spleen (m_spleen_01) program of the gentle-MACS Dissociator.B and T cell subsets phenotyping were quantified using flow cytometry.Results: Endocervix and ectocervix tissue was obtained from 4/6 recruited participants and two participants only had endocervix tissue available.Overall, T cell subsets (as marked by CD3+ and CD4+ subsets) were the most abundant cell population compared to B cells (as marked by CD19+ expression) in the cervix (45% vs. 4%, respectively).Although the overall frequency of B cells observed in both endocervical and ectocervical regions was low, the abundance of CD19+ cells was slightly higher in the endocervix (4%) compared to the ectocervix (2%).There was no significant difference in the frequencies of T cell populations (CD3+ and CD4+ cells) in the ectocervix and endocervix.The majority of CD4+ T cell co-receptors found in the cervix were CXCR4 (69%), followed by CD127 (67%), CXCR3 (66%) and CCR6 (63%).CCR5 was detected in 38%, while both CD25 and PD1 were expressed in 34% of CD4+ T cells.None of these CD4+ T cell co-receptors were significantly different in the ectocervix and endocervix, with an exception of CCR6 and PD1 that showed a trend towards being elevated in the endocervix compared to ectocervix, p=0.067.There was no difference in frequencies of both B and T cells amongst women on hormonal contraceptives versus non-hormonal contraceptive users.Discussion: Although limited by sample size, our data suggest that the T cells (CD3 and CD4+) were more abundant than B cells in the endocervix.Compared to the ectocervix, the endocervix had slightly higher frequencies of CD4+ T cell receptors (CCR6, PD-1, CCR5, CD25) suggesting that endocervix might be a preferential region for HIV infectivity, replication and transmission.
Author: N. Neelakanta Pillay
Language: English
Topic: HIV Research and Treatment
Subfield: Virology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: green
Funder: Inyuvesi Yakwazulu-Natali
OpenAlex ID: W2965967434