Increased expression of the natural killer cell inhibitory receptor CD85j/ILT2 on antigen-specific effector CD8 T cells and its impact on CD8 T-cell function

M Nedim Ince; Brooke Harnisch; Zhan Xu; Sang-Kyung Lee; Christoph Lange; Lorenzo Moretta; Michael Lederman; Judy Lieberman

doi:10.1046/j.1365-2567.2004.01907.x

Back

Increased expression of the natural killer cell inhibitory receptor CD85j/ILT2 on antigen-specific effector CD8 T cells and its impact on CD8 T-cell function

Journal article

Open access

Peer reviewed

Increased expression of the natural killer cell inhibitory receptor CD85j/ILT2 on antigen-specific effector CD8 T cells and its impact on CD8 T-cell function

M Nedim Ince, Brooke Harnisch, Zhan Xu, Sang-Kyung Lee, Christoph Lange, Lorenzo Moretta, Michael Lederman and Judy Lieberman

Immunology, Vol.112(4), pp.531-542

08/2004

DOI: 10.1046/j.1365-2567.2004.01907.x

PMCID: PMC1782522

PMID: 15270723

Files and links (1)

url

https://doi.org/10.1046/j.1365-2567.2004.01907.xView

Published (Version of record) Open Access

Abstract

We investigated whether inhibitory natural killer cell receptor (iNKR) expression contributes to impaired antigen-specific cytotoxicity and interferon-gamma (IFN-gamma) production by CD8 T cells during chronic infection. iNKR immunoglobulin-like transcript-2 (ILT2/CD85j) is expressed on 40-55% of cytomegalovirus (CMV)-, Epstein-Barr virus (EBV)- and human immunodeficiency virus (HIV)-specific CD8 T cells in both healthy and HIV-infected donors. Other iNKRs (CD158a, b1, e1/e2, k, CD94/NKG2A) are expressed on only a small minority of CD8 T cells and are not preferentially expressed on tetramer-staining virus-specific cells. In normal donors, ILT2 is expressed largely on perforin(+) CD27(-) effector cells. However, in HIV-infected donors, only a third of ILT2(+) cells are also perforin(+). In both normal and HIV-infected donors, ILT2(+) cells are prone to spontaneous apoptosis. Therefore, ILT2 is normally expressed during effector cytotoxic T-lymphocyte (CTL) differentiation, but can also be expressed when effector maturation is incomplete, as in HIV infection. The effect of ILT2 on CD8 cell function was assessed by preincubating effector cells with ILT2 antibody. While blocking ILT2 engagement has no appreciable effect on cytotoxicity, it increases antiviral IFN-gamma production by approximately threefold in both normal and HIV-infected donors. Thus, ILT2 expression, increased on antiviral CD8 cells in chronic infection, may interfere with protective CD8 T-cell function by suppressing IFN-gamma production.

Leukocyte Immunoglobulin-like Receptor B1

Membrane Glycoproteins - metabolism

Humans

Antigens, CD - metabolism

Cell Differentiation - immunology

HIV Infections - immunology

Lymphocyte Activation - immunology

Apoptosis - immunology

Pore Forming Cytotoxic Proteins

Epitopes, T-Lymphocyte - immunology

CD8-Positive T-Lymphocytes - immunology

Perforin

Interferon-gamma - biosynthesis

Receptors, Immunologic - metabolism

Cytotoxicity, Immunologic

Details

Title: Subtitle: Increased expression of the natural killer cell inhibitory receptor CD85j/ILT2 on antigen-specific effector CD8 T cells and its impact on CD8 T-cell function
Creators: M Nedim Ince - CBR Institute for Biomedical Research and Department of Pediatrics, Harvard Medical School, 200 Longwood Avenue, Boston, MA 02115, USA
Brooke Harnisch
Zhan Xu
Sang-Kyung Lee
Christoph Lange
Lorenzo Moretta
Michael Lederman
Judy Lieberman
Resource Type: Journal article
Publication Details: Immunology, Vol.112(4), pp.531-542
DOI: 10.1046/j.1365-2567.2004.01907.x
PMID: 15270723
PMCID: PMC1782522
NLM abbreviation: Immunology
ISSN: 0019-2805
eISSN: 1365-2567
Grant note: AI 36219 / NIAID NIH HHS AI 42519 / NIAID NIH HHS P30 AI036219 / NIAID NIH HHS R01 AI042519 / NIAID NIH HHS
Language: English
Date published: 08/2004
Academic Unit: Gastroenterology and Hepatology; Internal Medicine
Record Identifier: 9984094738902771

Metrics

25 Record Views

47 Times Cited - Web of Science