The Cellular Response Associated with Cervical Intraepithelial Neoplasia in HIV+and HIV-Subjects

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Abstract
This study investigates local alterations in T-cell and macrophage subsets that occur in cervical epithelial neoplasia (CIN), in the presence and absence of human immunodeficiency virus (HIV) infection. Ectocervical biopsies from 10 women with CIN who were infected with HIV, and 10 women with CIN but no HIV infection were studied by immunocytochemistry. Significantly increased proportions of activated CD8+ T cells were seen in all CIN biopsies, and these proportions were further increased in the presence of HIV infection. Levels of CD8+TIA-1+ cells were particularly increased in the CIN+HIV+ group. There was a lack of expression of CD28 on the CD8+ cells of the epithelium of CIN+HIV+ samples. A significant reduction in the proportion of epithelial inductive D1+ macrophages and an increase in D1+D7+-suppressive cells were observed in the CIN+HIV+ cohort. The lack of expression of CD28 on the CD8+ cells of the epithelium of CIN+HIV+ samples in combination with the reduced CD4+ T-cell numbers seen in the presence of HIV infection may contribute to the development of higher grade CIN in this susceptible group. This may be aggravated by the reduction in the D1+ epithelial inductive macrophages, which might reflect recruitment of more suppressive D1+D7+ cells. This would further compromise the ability of the local T-cell system to respond to antigens and thus contribute to the development of neoplasia at this site. These results suggest that the increase in activated CD8+ T cells is a consequence rather than a cause of CIN.