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Volume 6 Supplement 3

AIDS Vaccine 2009

  • Oral presentation
  • Open Access

OA031-04. Impairment of HIV-1-specific CD8+ T cell function by soluble epithelial adhesion molecules

  • H Streeck1,
  • D Kwon1,
  • JS Jolin1,
  • K Trocha1,
  • M Chevalier1,
  • T Caron2,
  • K Law2,
  • A Pyo1,
  • I Toth1,
  • DE Kaufmann1,
  • SJ Rodig2,
  • BD Walker1 and
  • M Altfeld1
Retrovirology20096(Suppl 3):O22

Published: 22 October 2009


Viral LoadViral ReplicationAntigenic StimulationIntracellular CytokineAbnormal Distribution


HIV-1-specific CD8+ T cell responses play an important role in the control over viral replication. Under persistent antigenic stimulation virus-specific CD8+ T cell become increasingly dysfunctional and upregulate several inhibitory molecules. The interaction and co-regulation of these molecules is largely unknown. The gastrointestinal associated lymphoid tissue (GALT) is one of the major sites of viral replication. Despite a substantial infiltration and expansion of HIV-1-specific CD8+ T cells in the GALT, viral replication appears to be more active in the GALT than in other body compartments. Here we show a distinct mechanism of inhibition of HIV-1-specific CD8+ T cells by soluble epithelial adhesion molecules with increasing viral loads in chronic HIV-1 infection.


HIV-infected individuals with chronic-progressive or chronic-controlled HIV-1 infection were analyzed. The distribution of E-cadherin in intestinal tissue was determined by immunohistochemistry. Plasma levels of soluble E-cadherin were determined using ELISA. Cytokine secretion by antigen-specific CD8+ T cells in the presence or absence of recombinant soluble E-cadherin was assessed by intracellular cytokine staining and Luminex.


HIV-1 infected individuals had abnormal distribution of E-cadherin in the intestinal mucosa relative to uninfected individuals. These subjects also had significantly increased soluble E-cadherin levels in the plasma relative to HIV-negative subjects (p < 0.05). The viral load in chronic HIV-1 infection correlated strongly with E-cadherin levels in the plasma (R = 0.7; p = 0.004). HIV-1-specific CD8+ T cells in subjects with chronic-progressive HIV-1 infection showed significant elevated levels of KLRG1 expression (p < 0.05). In the presence of soluble E-cadherin, a natural ligand for KLRG1, KLRG1hi HIV-1-specific CD8+ T cells showed reduced amounts of cytokine production upon antigenic stimulation, while KLRG1lo expressing cells were not affected.


Our data suggest a novel mechanism by which the disruption of the gastrointestinal epithelium leads to release of soluble E-cadherin, which specifically inhibits KLRG1hi expressing HIV-1-specific CD8+ T cells.

Authors’ Affiliations

Ragon Institute of MGH, MIT and Harvard, Charlestown, USA
Brigham and Women's Hospital, Boston, USA


© Streeck et al; licensee BioMed Central Ltd. 2009

This article is published under license to BioMed Central Ltd.