BTLA mediates inhibition of human tumor-specific CD8+ T cells that can be partially reversed by vaccination.

Details

Ressource 1Download: BIB_D0FCA4850407.P001.pdf (2614.17 [Ko])
State: Public
Version: Final published version
Serval ID
serval:BIB_D0FCA4850407
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
BTLA mediates inhibition of human tumor-specific CD8+ T cells that can be partially reversed by vaccination.
Journal
Journal of Clinical Investigation
Author(s)
Derré L., Rivals J.P., Jandus C., Pastor S., Rimoldi D., Romero P., Michielin O., Olive D., Speiser D.E.
ISSN
1558-8238[electronic], 0021-9738[linking]
Publication state
Published
Issued date
2010
Volume
120
Number
1
Pages
157-167
Language
english
Abstract
The function of antigen-specific CD8+ T cells, which may protect against both infectious and malignant diseases, can be impaired by ligation of their inhibitory receptors, which include CTL-associated protein 4 (CTLA-4) and programmed cell death 1 (PD-1). Recently, B and T lymphocyte attenuator (BTLA) was identified as a novel inhibitory receptor with structural and functional similarities to CTLA-4 and PD-1. BTLA triggering leads to decreased antimicrobial and autoimmune T cell responses in mice, but its functions in humans are largely unknown. Here we have demonstrated that as human viral antigen-specific CD8+ T cells differentiated from naive to effector cells, their surface expression of BTLA was gradually downregulated. In marked contrast, human melanoma tumor antigen-specific effector CD8+ T cells persistently expressed high levels of BTLA in vivo and remained susceptible to functional inhibition by its ligand herpes virus entry mediator (HVEM). Such persistence of BTLA expression was also found in tumor antigen-specific CD8+ T cells from melanoma patients with spontaneous antitumor immune responses and after conventional peptide vaccination. Remarkably, addition of CpG oligodeoxynucleotides to the vaccine formulation led to progressive downregulation of BTLA in vivo and consequent resistance to BTLA-HVEM-mediated inhibition. Thus, BTLA activation inhibits the function of human CD8+ cancer-specific T cells, and appropriate immunotherapy may partially overcome this inhibition.
Keywords
Animals, Antigens, CD/physiology, Antigens, Neoplasm/immunology, Apoptosis Regulatory Proteins/physiology, CD8-Positive T-Lymphocytes/immunology, COS Cells, Cell Line, Tumor, Cercopithecus aethiops, Humans, Interferon-gamma/biosynthesis, Lymphocyte Activation, MART-1 Antigen, Melanoma/immunology, Melanoma/therapy, Neoplasm Proteins/immunology, Oligodeoxyribonucleotides/pharmacology, Receptors, Immunologic/physiology, Receptors, Tumor Necrosis Factor, Member 14/physiology, Vaccination
Pubmed
Web of science
Open Access
Yes
Create date
08/01/2010 14:44
Last modification date
20/08/2019 15:51
Usage data