Primary HIV-1 Infection Is Associated with Preferential Depletion of CD4+ T Lymphocytes from Effector Sites in the Gastrointestinal Tract

TLDR

The gastrointestinal mucosa, rich in CCR5‑expressing, immunologically activated CD4⁺ T cells, is uniquely vulnerable to HIV‑1 infection and its role in disease progression warrants further investigation. The study sought to determine whether primary HIV‑1 infection preferentially depletes mucosal CD4⁺ T cells, to identify the anatomic subcompartment of depletion, and to assess whether fully suppressive HAART can restore mucosal immunity. During primary infection, mucosal CD4⁺ T cells are significantly and preferentially depleted compared with peripheral blood, mainly in the effector subcompartment while the inductive compartment retains HIV‑1 RNA; even after up to five years of fully suppressive therapy, peripheral blood CD4⁺ T cells recover nearly completely, but a substantial loss persists in the gastrointestinal mucosa.

Abstract

Given its population of CCR5-expressing, immunologically activated CD4+ T cells, the gastrointestinal (GI) mucosa is uniquely susceptible to human immunodeficiency virus (HIV)-1 infection. We undertook this study to assess whether a preferential depletion of mucosal CD4+ T cells would be observed in HIV-1–infected subjects during the primary infection period, to examine the anatomic subcompartment from which these cells are depleted, and to examine whether suppressive highly active antiretroviral therapy could result in complete immune reconstitution in the mucosal compartment. Our results demonstrate that a significant and preferential depletion of mucosal CD4+ T cells compared with peripheral blood CD4+ T cells is seen during primary HIV-1 infection. CD4+ T cell loss predominated in the effector subcompartment of the GI mucosa, in distinction to the inductive compartment, where HIV-1 RNA was present. Cross-sectional analysis of a cohort of primary HIV-1 infection subjects showed that although chronic suppression of HIV-1 permits near-complete immune recovery of the peripheral blood CD4+ T cell population, a significantly greater CD4+ T cell loss remains in the GI mucosa, despite up to 5 yr of fully suppressive therapy. Given the importance of the mucosal compartment in HIV-1 pathogenesis, further study to elucidate the significance of the changes observed here is critical.