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

Abstract

Given its population of CCR5-expressing, immunologically activated CD4 ϩ 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 ϩ 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 ϩ T cells compared with peripheral blood CD4 ϩ T cells is seen during primary HIV-1 infection. CD4 ϩ 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 ϩ T cell population, a significantly greater CD4 ϩ 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.

Microbial Translocation in the Pathogenesis of HIV Infection and AIDS

“…Several months later, those authors reported significantly increased levels of circulating LPS in both chronically HIV-infected individuals and SIV-infected rhesus macaques (RM) that positively correlated with measures of innate and adaptive immune activation (33). After that initial report, numerous studies have confirmed that HIV infection is associated with a substantial loss of CD4 ϩ T cells residing in the gut, in turn leading to microbial translocation (34,35).…”

Effect of Antiretroviral Therapy on Apoptosis Markers and Morphology in Peripheral Lymph Nodes of HIV-Infected Individuals

“…During early infection, the cell destruction involves primarily CCR5+ effector memory T cells and occurs predominantly in the mucosal tissue, particularly in the intestinal immune system [15,16]. Disordered apoptosis and an increased rate of activation-induced cell death (AICD) lead to destabilization and progressive change of the homeostasis of resting naive and memory T cell populations [14,[17][18][19][20].…”

Differential cross-reactivity of monoclonal antibody OPD4 (anti-CD45RO) in macaques

“…The ability to distinguish naïve and memory subsets in macaques led to the discovery that simian immunodeficiency virus rapidly and selectively infects and eliminates "memory" CD4+ T cells, particularly in mucosal tissues [1][2][3], findings that were recently confirmed in HIV-infected patients [4,5]. These findings have revolutionized our understanding of HIV pathogenesis by demonstrating that HIV *Corresponding author: RS Veazey, Tulane National Primate Research Center, 18703 Three Rivers Road, Covington, LA 70433, Phone (985) 871-6228, Fax (985) 871-6510, Email: rveazey@tulane.edu.…”