COMPARATIVE INVESTIGATION OF LANGERHANS CELLS AND POTENTIAL RECEPTORSFOR HIV IN ORAL, GENITOURINARY AND RECTAL EPITHELIA

Human immunodeficiency virus (HIV) is commonly transmitted, during hom osexual and heterosexual intercourse, through the rectal and cervicova ginal mucosa, foreskin and urethral epithelia. However, there is uncer tainty about HIV transmission through the oral mucosa by oral sex. We have carried out a comparative immunohistological investigation of pri mate oral, cervicovaginal, foreskin, urethral and rectal epithelia for potential HIV receptors. We investigated epithelial tissues for CD4 g lycoprotein, which is the principal receptor for HIV, Fc receptors of IgG for binding HIV-IgG antibody complexes, and HLA class II, which mi ght enable HIV-bound CD4(+) cells to gain access to the epithelial cel ls. CD4 glycoprotein was not found in oral, foreskin, urethral, vagina l or rectal epithelial cells, although CD4(+) mononuclear cells were p resent in the lamina propria of each epithelium. Fc gamma II and Fc ga mma III receptors were found in urethral, endocervical and rectal epit helia, and Fc gamma III and Fc gamma I receptors in the foreskin. Howe ver, Fc gamma receptors were not found in oral epithelium (buccal, lab ial, lingual or palatal) and only Fc gamma III receptors were detected in the gingival epithelial cells. HLA class II antigen was also not d etected in foreskin, oral or rectal epithelium, but it was expressed b y endocervical cells from most human specimens and in male urethral ep ithelia of non-human male primates. Langerhans' cells were found in al l epithelia except those of the urethra and rectum, and they can expre ss 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 epitheli um or foreskin. The HIV-binding V1 domain of CD4 was significantly dec reased in Langerhans' cells present in oral compared with vaginal epit helium. The results suggest that the foreskin in uncircumcised men and the cervicovaginal epithelium in females might become infected via th e CD4(+) Langerhans' cells. However, urethral infection might be media ted by HIV-antibody complexes binding to urethral epithelial Fc gamma receptors. The paucity of Langerhans' cells expressing the V1 domain o f CD4, the absence of Fc gamma receptors, and a lack of expression of HLA class II antigens in most oral epithelial cells, argue against tra nsmission of HIV through the normal intact oral mucosa.