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Human immunodeficiency virus (HIV) is commonly transmitted, during homosexual and heterosexual intercourse, through the rectal and cervicovaginal mucosa, foreskin and urethral epithelia. However, there is uncertainty about HIV transmission through the oral mucosa by oral sex. We have carried out a comparative immunohistological investigation of primate oral, cervicovaginal, foreskin, urethral and rectal epithelia for potential HIV receptors. We investigated epithelial tissues for CD4 glycoprotein, which is the principal receptor for HIV, Fc receptors of IgG for binding HIV-IgG antibody complexes, and HLA class II, which might enable HIV-bound CD4+ cells to gain access to the epithelial cells. CD4 glycoprotein was not found in oral, foreskin, urethral, vaginal or rectal epithelial cells, although CD4+ mononuclear cells were present in the lamina propria of each epithelium. Fc gamma II and Fc gamma III receptors were found in urethral, endocervical and rectal epithelia, and Fc gamma III and Fc gamma I receptors in the foreskin. However, Fc gamma receptors were not found in oral epithelium (buccal, labial, lingual or palatal) and only Fc gamma III receptors were detected in the gingival epithelial cells. HLA class II antigen was also not detected in foreskin, oral or rectal epithelium, but it was expressed by endocervical cells from most human specimens and in male urethral epithelia of non-human male primates. Langerhans' cells were found in all epithelia except those of the urethra and rectum, and they can express CD4 glycoprotein, Fc gamma receptors and HLA class II antigen. The mean number of Langerhans' cells expressing CD4 in the upper third of oral epithelium was significantly lower compared with vaginal epithelium or foreskin. The HIV-binding V1 domain of CD4 was significantly decreased in Langerhans' cells present in oral compared with vaginal epithelium. The results suggest that the foreskin in uncircumcised men and the cervicovaginal epithelium in females might become infected via the CD4+ Langerhans' cells. However, urethral infection might be mediated by HIV-antibody complexes binding to urethral epithelial Fc gamma receptors. The paucity of Langerhans' cells expressing the V1 domain of CD4, the absence of Fc gamma receptors, and a lack of expression of HLA class II antigens in most oral epithelial cells, argue against transmission of HIV through the normal intact oral mucosa.

Rectal and cervicovaginal mucosa are common routes of transmission of HIV, although the mechanism of transmission is unknown. We have investigated human rectal and cervicovaginal epithelia for the expression of complement receptors (CR) and cell adhesion molecules which may be involved in HIV and other infections. In rectal mucosa, CR3 was detected in the surface and crypt epithelial cells by immunohistology, using MoAbs to CD18 and CD11b in 10 out of 15 specimens. RNA transcripts encoding both CD11b and CD18 were also demonstrated in surface and crypt epithelial cells by in situ hybridization. Although CD11b was detected in the epithelial cells in three out of the 14 cervicovaginal specimens, we were unable to detect CD18. We suggest that expression of the CD11b/CD18 heterodimer might facilitate transmission of HIV by enhancing binding of HIV-antibody complexes in seminal fluid to epithelial cells. Alternatively, since intercellular adhesion molecule-1 (ICAM-1) is a receptor for CD11b/CD18, this may promote adhesion between epithelial cells and HIV-infected mononuclear cells in seminal fluid. [ABSTRACT FROM AUTHOR]

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 lot HIV and Langerhans cells and the related dendritic cells could play a role in the initial transmission of HIV. For 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 epithelial 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 IL, FcγR2 and FcγR3 were detected in most vaginal, ectocervical and transformation zone epithelia and in 9/14 endocervicul 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 FcγR1 was not detected. We then demonstrated mRNA for FcγR3 in the columnar endocervical epithelial cells and transformation zone by in situ hybridization using a CDl6-RNA probe. FcγR3 and FcγR2 gene transcripts were also found in fetal cervical tissue by applying the polymerase chain reaction to amplify portions of the FcγRl 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, Fey 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 IT antigen which may infect these or the adjacent CD4+ cells. [ABSTRACT FROM AUTHOR]