MUCOSAL MACROPHAGE SUBSETS OF THE GUT IN HIV - DECREASE IN ANTIGEN-PRESENTING CELL PHENOTYPE

The effect of HIV infection on intestinal lamina propria macrophage su bsets was investigated in 41 patients at various stages of HIV infecti on (asymptomatic HIV infection, n = 17; AIDS, n = 24). Duodenal biopsi es taken from HIV patients at endoscopy were snap frozen and cryostat sections cut for immunohistochemical staining. MoAbs CD68 (EBM11, pan- macrophage marker), RFD1 (antigen-presenting cells) and RFD7 (mature p hagocytic macrophages) were used to identify cell subsets using indire ct immunoperoxidase or alkaline phosphatase. Double immunofluorescence using MoAbs to HIV proteins (p24, p17 and gp120) and RFD1 were used t o identify HIV-infected antigen-presenting cells. Double immunofluores cence was also used to identify macrophages that expressed both RFD1 a nd RFD7 ('suppressor' macrophages). Intensity of HLA-DR expression in lamina propria cells was investigated using a MoAb to HLA-DR directly conjugated to glucose oxidase. The results show that there was no diff erence in overall density of macrophages, but there was a significant decrease in dendritic cells (RFD1+) in all clinical stages of HIV. The re was no difference in the density of RFD7+ macrophages, nor was ther e a difference in intensity of HLA-DR expression in lamina propria cel ls. Only four HIV-infected cells were positively identified in the 41 patients. This result suggests that the antigen-presenting arm of muco sal immune defences may be seriously compromised in HIV infection, and represents a further insult to mucosal immunity already impaired as a result of loss of CD4+ T lymphocytes. This may contribute to developm ent of opportunist infection in the gut.