Th17 Cells Coordinate with Th22 Cells in Maintaining Homeostasis of Intestinal Tissues and both are Depleted in SIV-Infected Macaques.

Huanbin Xu

doi:10.4172/2155-6113.1000302

Abstract

Th17 and Th22 cells are thought to function as innate regulators of mucosal antimicrobial responses, tissue inflammation and mucosal integrity, yet their role in persistent SIV infection is still unclear. Here we compared Th17 and Th22 cells in their phenotype, effector/cytokine function, and frequency in blood and intestinal mucosal tissues, and correlate levels with mucosal damage in SIV-infected rhesus macaques. We found that Th17/Th22 cells share similar features in that both highly produce TNF-α and IL-2 and express CCR5 in intestinal tissues; yet very few show cytotoxic functions, as evidenced by lack of IFN-γ and granzyme B production. Further, Th17/Th22 cells display distinct tissue-specific distributions. Both Th17 and Th22 cells and cytokine secretion were significantly depleted in both blood and intestine in chronically SIV-infected macaques. The frequency of Th17 and Th22 cells in the intestine positively correlated with percentages of intestinal CD4+ T cells and negatively with damage to intestinal mucosa, and plasma viral loads in SIV infection. These findings indicate Th17 and Th22 cells share considerable functions, and may coordinate in innate mucosal immune responses, and their regional loss in the intestine may be associated with local mucosal immune dysfunction in persistent HIV/SIV infection.

Highlights

Progressive human immunodeficiency virus (HIV) and simian immunodeficiency virus (SIV) infection is characterized by massive, early loss of CD4 T cells from the intestinal mucosa, as well as by structural disruption of the gut barrier and increased microbial translocation [1,2,3,4]
We show both IL-17 and IL-22 promote intestinal epithelial survival in vitro. These findings suggest that Th17 cells functionally cooperate with Th22 cells, and both appear critical in maintaining innate immunity and regulating homeostasis of the gut barrier in HIV/SIV infection
Th17 and Th22 cells were defined here defined based on CD3+CD4+ expression, and their ability to produce IL-17 or/and IL-22, and levels of each subset were compared in peripheral blood and intestinal tissues of normal macaques

Summary

Introduction

Progressive human immunodeficiency virus (HIV) and simian immunodeficiency virus (SIV) infection is characterized by massive, early loss of CD4 T cells from the intestinal mucosa, as well as by structural disruption of the gut barrier and increased microbial. Th17 cells are maintained at relatively normal levels in the GI tract of SIV-infected natural host species, HIV-infected long-term nonprogressors, as well as some patients on antiviral therapy [8,9,10,11]. Loss of intestinal Th17 and Th22 cells correlated with reductions in intestinal CD4+ T cells during SIV infection, accompanied by damage to the mucosal barrier We show both IL-17 and IL-22 promote intestinal epithelial survival in vitro. These findings suggest that Th17 cells functionally cooperate with Th22 cells, and both appear critical in maintaining innate immunity and regulating homeostasis of the gut barrier in HIV/SIV infection

Results

Discussion

Experimental Procedures