Expression and gene transcript of Fc receptors for IgG, HLA class II antigens and Langerhans cells in human cervico-vaginal epithelium

Abstract

SUMMARY: The mechanism of transmission of HIV from the male to the female genital tract or in the reverse order is not clear. CD4 glycoprotein is the receptor for HIV and Langerhans cells and the related dendritic cells could play a role in the initial transmission of HIV. Fc receptors (FcR) for IgG might be involved in antibody-mediated binding of HIV. We carried out an immunohistological study of normal human cervical and vaginal epithelia for the presence of CD4 glycoprotein, Langerhans cells and FcR to IgG. CD4+ glycoprotein was not found in the vaginal or cervical epithelium, with the exception of a few endocervical epithelial cells. A small number of CD4+ mononuclear cells were found in the endocervical epithelium of a third of the specimens but a large number of CD4+ cells was found in the submucosa of most of the cervical and vaginal specimens. Langerhans cells expressing CD4, HLA class II, FcγR2 and FcγR3 were detected in most vaginal, ectocervical and transformation zone epithelia and in 9/14 endocervical tissues. FcγR3 was detected in about two-thirds of the columnar endocervical epithelium and the transformation zone. A smaller number of specimens expressed FcγR2 in these epithelia, but FcγRl was not detected. We then demonstrated mRNA for FcγR3 in the columnar endocervical epithelial cells and transformation zone by in situ hybridization, usinga CD16-RNA probe. FeγR3 and FcγR2 gene transcripts were also found in fetal cervical tissue by applying the polymerase chain reaction to amplify portions of the FcγR3 and FcγR2 coding sequences in cDNA prepared from fetal RNA. HLA-DR was found in the endocervical cells, transformation zone and in Langerhans cells of all specimens. The presence of Langerhans cells, Fcγ receptors and HLA class II antigen offers three potential mechanisms for cervico-vaginal HIV transmission: (i) direct HIV infection of Langerhans cells, (ii) binding of HIV antibody complexes to cervical epithelial Fcγ receptors and (iii) binding of HIV infected CD4+ cells to cervical HLA class II antigen which may infect these or the adjacent CD4+ cells.