Extended co-expression of inhibitory receptors by human CD8 T-cells depending on differentiation, antigen-specificity and anatomical localization.

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State: Public
Version: Final published version
Serval ID
serval:BIB_3FF2F389E966
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Extended co-expression of inhibitory receptors by human CD8 T-cells depending on differentiation, antigen-specificity and anatomical localization.
Journal
PLoS One
Author(s)
Baitsch L., Legat A., Barba L., Fuertes Marraco S.A., Rivals J.P., Baumgaertner P., Christiansen-Jucht C., Bouzourene H., Rimoldi D., Pircher H., Rufer N., Matter M., Michielin O., Speiser D.E.
ISSN
1932-6203 (Electronic)
ISSN-L
1932-6203
Publication state
Published
Issued date
2012
Volume
7
Number
2
Pages
e30852
Language
english
Abstract
Inhibitory receptors mediate CD8 T-cell hyporesponsiveness against cancer and infectious diseases. PD-1 and CTLA-4 have been extensively studied, and blocking antibodies have already shown clinical benefit for cancer patients. Only little is known on extended co-expression of inhibitory receptors and their ligands. Here we analyzed the expression of eight inhibitory receptors by tumor-antigen specific CD8 T-cells. We found that the majority of effector T-cells simultaneously expressed four or more of the inhibitory receptors BTLA, TIM-3, LAG-3, KRLG-1, 2B4, CD160, PD-1 and CTLA-4. There were major differences depending on antigen-specificity, differentiation and anatomical localization of T-cells. On the other hand, naive T-cells were only single or double positive for BTLA and TIM-3. Extended co-expression is likely relevant for effector T-cells, as we found expression of multiple ligands in metastatic lesions of melanoma patients. Together, our data suggest that naive T-cells are primarily regulated by BTLA and TIM-3, whereas effector cells interact via larger numbers of inhibitory receptors. Blocking multiple inhibitory receptors simultaneously or sequentially may improve T-cell based therapies, but further studies are necessary to clarify the role of each receptor-ligand pair.
Pubmed
Web of science
Open Access
Yes
Create date
12/05/2012 9:11
Last modification date
20/08/2019 13:37
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