The distribution of immunocompetent cells in the genital tract of HIV-positive women

Abstract

Objective: To study the distribution of immunocompetent cells in the female lower genital tract and to determine whether it is altered in HIV infection.

Methods: Colposcopically directed cervical biopsies were taken in the premenstrual phase of 10 HIV-positive women with sexually acquired infection, and matched HIV-negative controls. Peripheral blood was collected from the HIV-infected group for immune studies. Histological, immunohistochemical and double immunofluorescence techniques were applied to the biopsies to reveal immunocompetent cell distribution. Comparisons were made between the immune cell populations in the cervix in the HIV-positive and negative groups, and between the cervix and peripheral blood in the HIV-positive group.

Results: Cervical biopsies from HIV-positive women had significantly reduced Langerhans and plasma cell counts in the submucosa, but increased T lymphocyte counts compared with the HIV-negative group. There was an increase in CD8+ lymphocyte numbers in cervical biopsies of HIV-positive women, causing an inversion of the CD4/CD8 ratio. The majority of these CD8+ cells were 'memory' (CD45RO+) cells, with reduced proportions expressing perforin (cytoplasmic cytolytic granules) and TIA-1 (cytolytic granule-associated protein). Natural killer (CD57) cell markers were not detected. The levels of CD8+ cells expressing Bcl-2 (a gene product inhibiting cell apoptosis) in HIV-positive women with relatively high peripheral CD4 lymphocyte cell counts was higher than in HIV-negative women, but these levels fell with declining CD4 lymphocyte counts (< 300 x 10(6)/1). The reduction in CD4/CD8 ratio in the cervix occurred even with relatively high peripheral CD4 counts.

Conclusions: HIV disease is associated with alterations in the proportions of immunocompetent cells in the cervix. There is an increase in CD8+ T-lymphocytes and evidence of reduced cytolytic capacity; thus, CD8+ cells may lack the ability to respond to viral infection. Reduction in Langerhans' and plasma cells may reflect loss of signals from CD4+ T cells. These findings may, in part, explain why HIV-infected women are susceptible to recurrent fungal and viral infections, even when peripheral immune function is intact. Further studies of immune cell function are urgently required to further elucidate these findings.