Anti-α4β7 therapy targets lymphoid aggregates in the gastrointestinal tract of HIV-1-infected individuals. Academic Article uri icon

Overview

abstract

  • Gut homing CD4+ T cells expressing the integrin α4β7 are early viral targets and contribute to HIV-1 pathogenesis, likely by seeding the gastrointestinal (GI) tract with HIV. Although simianized anti-α4β7 monoclonal antibodies have shown promise in preventing or attenuating the disease course of simian immunodeficiency virus in nonhuman primate studies, the mechanisms of drug action remain elusive. We present a cohort of individuals with mild inflammatory bowel disease and concomitant HIV-1 infection receiving anti-α4β7 treatment. By sampling the immune inductive and effector sites of the GI tract, we have discovered that anti-α4β7 therapy led to a significant and unexpected attenuation of lymphoid aggregates, most notably in the terminal ileum. Given that lymphoid aggregates serve as important sanctuary sites for maintaining viral reservoirs, their attrition by anti-α4β7 therapy has important implications for HIV-1 therapeutics and eradication efforts and defines a rational basis for the use of anti-α4β7 therapy in HIV-1 infection.

authors

publication date

  • October 3, 2018

Research

keywords

  • Gastrointestinal Tract
  • HIV Infections
  • Integrins
  • Lymphoid Tissue

Identity

PubMed Central ID

  • PMC6314200

Scopus Document Identifier

  • 85054425247

Digital Object Identifier (DOI)

  • 10.1126/scitranslmed.aau4711

PubMed ID

  • 30282696

Additional Document Info

volume

  • 10

issue

  • 461