Enhanced levels of functional HIV-1 co-receptors on human mucosal T cells demonstrated using intestinal biopsy tissue

Objective: To examine compartmental differences in co-receptor expression o n CD4 lymphocytes between blood and gut using endoscopic biopsies. Design: Mucosal and peripheral CD4 T cells from healthy controls were compa red For co-receptor expression and vulnerability to infection by HIV-1. Methods: Expression of CCR5 and CXCR4 was quantified by flow cytometry on i solated mucosal CD4 lymphocytes obtained from endoscopic biopsies and blood from healthy controls. Vulnerability to in vitro infection by both R5 and X4 strains was assessed by measuring p24. Results: Biopsies yielded sufficient lymphocytes for flow cytometric charac terization and infectivity studies. The percentage of mucosal CD4 T lymphoc ytes that expressed CCR5 and the per cell expression of CCR5 were both sign ificantly increased compared with that in peripheral blood CD4 T lymphocyte s. CXCR4 was expressed on the majority of CD4, lymphocytes in both compartm ents. In vitro infection of mucosal mononuclear cells supported greater vir al replication of both R5 and X4 strains than peripheral blood mononuclear cells. Conclusions: Enhanced expression of CXCR4 and CCR5 on CD4 lymphocytes in no rmal intestinal mucosa predicts increased vulnerability to infection by bot h R5 and X4 HIV-1. Endoscopic biopsies provide a useful mucosal tissue samp ling technique to identify compartmental immunologic differences that may b e exploited by HIV-1 in establishing initial mucosal infection. (C) 2000 Li ppincott Williams & Wilkins.