Epithelial adhesion molecules can inhibit HIV-1-specific CD8⁺ T-cell functions.

Details

Serval ID
serval:BIB_DEABC84F4EF8
Type
Article: article from journal or magazin.
Collection
Publications
Title
Epithelial adhesion molecules can inhibit HIV-1-specific CD8⁺ T-cell functions.
Journal
Blood
Author(s)
Streeck H., Kwon D.S., Pyo A., Flanders M., Chevalier M.F., Law K., Jülg B., Trocha K., Jolin J.S., Anahtar M.N., Lian J., Toth I., Brumme Z., Chang J.J., Caron T., Rodig S.J., Milner D.A., Piechoka-Trocha A., Kaufmann D.E., Walker B.D., Altfeld M.
ISSN
1528-0020 (Electronic)
ISSN-L
0006-4971
Publication state
Published
Issued date
12/05/2011
Peer-reviewed
Oui
Volume
117
Number
19
Pages
5112-5122
Language
english
Notes
Publication types: Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Abstract
Under persistent antigenic stimulation, virus-specific CD8⁺ T cells become increasingly dysfunctional and up-regulate several inhibitory molecules such as killer lectin-like receptor G1 (KLRG1). Here, we demonstrate that HIV-1 antigen-specific T cells from subjects with chronic-progressive HIV-1 infection have significantly elevated KLRG1 expression (P < .001); show abnormal distribution of E-cadherin, the natural ligand of KLRG1, in the intestinal mucosa; and have elevated levels of systemic soluble E-cadherin (sE-cadherin) that significantly correlate with HIV-1 viral load (R = 0.7, P = .004). We furthermore demonstrate that in the presence of sE-cadherin, KLRG1(hi) HIV-1-specific CD8⁺ T cells are impaired in their ability to respond by cytokine secretion on antigenic stimulation (P = .002) and to inhibit viral replication (P = .03) in vitro. Thus, these data suggest a critical mechanism by which the disruption of the intestinal epithelium associated with HIV-1 leads to increased systemic levels of sE-cadherin, which inhibits the effector functions of KLRG1(hi)-expressing HIV-1-specific CD8⁺ T cells systemically.
Keywords
CD8-Positive T-Lymphocytes/immunology, CD8-Positive T-Lymphocytes/metabolism, Cadherins/immunology, Cadherins/metabolism, Cell Adhesion Molecules/immunology, Cell Adhesion Molecules/metabolism, Cell Separation, Colon/immunology, Colon/metabolism, Enzyme-Linked Immunosorbent Assay, Female, Flow Cytometry, Fluorescent Antibody Technique, HIV Infections/immunology, HIV Infections/metabolism, HIV-1/immunology, Humans, Immunohistochemistry, Lectins, C-Type/biosynthesis, Lectins, C-Type/immunology, Lymphocyte Activation/immunology, Male, Receptors, Immunologic, Trans-Activators/biosynthesis, Trans-Activators/immunology, Virus Replication/immunology
Pubmed
Web of science
Open Access
Yes
Create date
09/05/2023 13:00
Last modification date
29/11/2024 13:31
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