Programmed death-1 expression and regulatory T cells increase in the Intestinal mucosa of cytomegalovirus colitis in patients with HIV/AIDS

Abstract

Background: Cytomegalovirus (CMV) is among the most common opportunistic infections identified in patients with HIV/AIDS. CMV often targets the colon in such patients. However, the role of regulatory T cells (Tregs) and Programmed death-1 (PD-1) in intestinal CMV infection is unclear. In this study, we evaluate the expression of programmed death -1 (PD-1) and its association with regulatory T cells (Tregs) in patients with HIV/AIDS having CMV colitis. Methods: CMV was detected in the intestinal mucosal biopsy samples via nucleic acid in situ hybridization. PD-1, CD4, CD8, and Treg-specific marker as well as the winged-helix transcription factor and forkhead box P3 (FoxP3) were detected by immunohistochemical methods. Results: Intestinal CMV diease was identified in 20 out of 195 patients with HIV/AIDS enrolled in our study. CMV was diagnosed microscopically by the presence of giant cell inclusion bodies in epithelial cells, histiocytes, and fibroblasts. Levels of immunoreactive PD-1 detected in mucosal biopsies from patients with HIV/AIDS having CMV colitis were significantly higher than CMV-negative control group (p = 0.023). FoxP3+ cells were detected in the CMV colitis group slight more than that in the control group. CD4+ T lymphocyte counts in the peripheral blood and intestinal mucosal biopsies from CMV colitis group were all notably decreased compared with those with control group (p < 0.001 for both). PD-1 had a significant negative correlation with CD4 counts in intestinal mucosa (p = 0.016). CD8+T lymphocyte counts in peripheral blood and intestinal mucosa were slightly lower than those in the control group, although the differences were not statistically significant. Conclusions: CMV colitis with HIV/AIDS is associated with significant changes in T lymphocyte populations. These findings may have important implications for disease pathogenesis and progression.