Depletion of stromal and intraepithelial antigen-presenting cells in cervical neoplasia in human immunodeficiency virus infection

Human immunodeficiency virus-positive (HIV+) women have an increased risk of lower genital tract dysplasia and neoplasia, and studies of the central lymphoid system suggest that impaired immunosurveillance plays a role in the development of their cervical tumors. Intraepithelial and stromal immunocompetent cell counts were compared in cervical specimens from 50 HIV+ and 50 appropriately matched HIV- women (controls) with low and high grade squamous intraepithelial lesions (SIL), or carcinoma. Each histological class of HIV+ women displayed fewer intraepithelial Langerhans' (S100+) cells (LC) (as already known), and also fewer stromal LC and both intraepithelial and stromal (CD68+) macrophages. LC and macrophages were reduced in all HIV+ patients, whereas reduction of cervical T lymphocytes was found in only immunocompromised subjects (peripheral blood CD4+ T-cell count <500/μL). A mucosal quantitative deficiency of antigen-presenting cells (APC) thus precedes that of T cells. HIV infection appears to lead to early impairment of mucosal immunoreactivity mainly because of defective antigen presentation. This impairment may be one mechanism underlying the increased frequency of cervical dysplasia/neoplasia, and the enhanced aggressiveness of invasive cancers in HIV+ women.