Ahmed, Shahla Mumtaz; (2007) The relationship of the immune system in the female lower genital tract to HIV infection and the emergence of CIN. Doctoral thesis , UCL (University College London).

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Abstract

There is a relative paucity of information about the immune system within the female lower genital tract. This study had three aims. Firstly, to investigate the distribution and function of immunocompetent cells within the ectocervix and to establish the components of humoral immunity within the normal female lower genital tract. Secondly, to determine the effects of HIV infection on these parameters. Thirdly, to identify alterations in cellular and humoral immunity in the context of cervical intraepithelial neoplasia, with and without HIV co-infection. Cervical tissue samples were studied using standard immunohistological techniques and cervicovaginal secretions were analysed by radial immunodiffusion, and by the ELISA method. Normal cervical tissue showed high proportions of primed memory CD4+ T-cells (CD45RO+) and cytotoxic CD8+ cells (CD8+TIA-1+). The majority of epithelial macrophages were of the inducer-type (D1+D7-) and the majority of stromal macrophages were mature phagocytes (D1-D7+) with very few suppressive macrophages (D1+D7+). Although the cytokines IL-ip, TNF-a and TGF-Pi were detected in vaginal secretions, only TNF-a appeared cell-associated in cervical tissues. Relatively high concentrations of IgG and IgA occurred in cervicovaginal secretions. This suggests that the normal female genital tract possesses a reactive immune system with a high proportion of primed activated cells. Cervical biopsies from HIV-infected women showed reversal of the CD4+:CD8+ T-cell ratio. Despite greater proportions of activated T-cells and epithelial macrophages, there was no increase in cytolytic potential. There was an increase in suppressive macrophages and a fall in Langerhans' cell numbers. These changes may facilitate the sexual transmission of HIV infection. The emergence of CIN was associated with greater proportions of activated and cytolytic T-cells. The CIN+HIV+ group showed lower epithelial inducer macrophage proportions and higher suppressive cells. The combination of these factors may contribute to the susceptibility of HIV-infected women to develop CIN, as well as to the rapid progression of CIN in this group.

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