Role of T-cell trafficking in the pathogenesis of HIV disease

Abstract

Purpose of review 

Trafficking of lymphocytes into and between gut inductive and effector sites of the gut tissues is regulated by integrin α₄β₇. Recent findings that describe the central role of α₄β₇^hi CD4⁺ T cells in HIV pathogenesis, and the possibility of targeting these cells to prevent or treat HIV infection will be reviewed.

Recent findings 

Recent reports indicate that the frequency of α₄β₇^hi CD4⁺ T cells is directly correlated with the risk of HIV acquisition and CD4⁺ T-cell decline post infection. MAdCAM -mediated signaling through α₄β₇, in the presence of retinoic acid, supports viral replication in recently activated naïve CD4⁺ T cells. Treatment of HIV-infected patients with vedolizumab, an α₄β₇ antagonist, is well tolerated, and reduces the size and number of lymphoid aggregates in gut associated lymphoid tissues.

Summary 

Integrin α₄β₇ underlies one of the principal mechanisms that CD4⁺ T cells employ to traffic to the gut. It also defines a subset of cells that play a significant role in HIV transmission and pathogenesis. Understanding how α₄β₇ facilitates gut homing may provide insight into key aspects of HIV transmission, pathogenesis, and the formation of viral reservoirs. Targeting α₄β₇ may have utility in the prevention and treatment of HIV infection.