- Oral presentation
- Open Access
- Published:
OA031-04. Impairment of HIV-1-specific CD8+ T cell function by soluble epithelial adhesion molecules
Retrovirology volume 6, Article number: O22 (2009)
Background
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.
Methods
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.
Results
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.
Conclusion
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.
Author information
Affiliations
Corresponding author
Correspondence to H Streeck.
Rights and permissions
Open Access This article is published under license to BioMed Central Ltd. This is an Open Access article is distributed under the terms of the Creative Commons Attribution 2.0 International License (https://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
About this article
Cite this article
Streeck, H., Kwon, D., Jolin, J. et al. OA031-04. Impairment of HIV-1-specific CD8+ T cell function by soluble epithelial adhesion molecules. Retrovirology 6, O22 (2009). https://doi.org/10.1186/1742-4690-6-S3-O22
Published:
Keywords
- Viral Load
- Viral Replication
- Antigenic Stimulation
- Intracellular Cytokine
- Abnormal Distribution
