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
Institution
Title
Epithelial adhesion molecules can inhibit HIV-1-specific CD8⁺ T-cell functions.
Journal
Blood
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
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
Publisher's website
Open Access
Yes
Create date
09/05/2023 13:00
Last modification date
29/11/2024 13:31