Title |
Extended Co-Expression of Inhibitory Receptors by Human CD8 T-Cells Depending on Differentiation, Antigen-Specificity and Anatomical Localization
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Published in |
PLOS ONE, February 2012
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DOI | 10.1371/journal.pone.0030852 |
Pubmed ID | |
Authors |
Lukas Baitsch, Amandine Legat, Leticia Barba, Silvia A. Fuertes Marraco, Jean-Paul Rivals, Petra Baumgaertner, Céline Christiansen-Jucht, Hanifa Bouzourene, Donata Rimoldi, Hanspeter Pircher, Nathalie Rufer, Maurice Matter, Olivier Michielin, Daniel E. Speiser |
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. |
Mendeley readers
Geographical breakdown
Country | Count | As % |
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United States | 4 | 2% |
Denmark | 1 | <1% |
Switzerland | 1 | <1% |
Japan | 1 | <1% |
Spain | 1 | <1% |
Unknown | 178 | 96% |
Demographic breakdown
Readers by professional status | Count | As % |
---|---|---|
Researcher | 55 | 30% |
Student > Ph. D. Student | 38 | 20% |
Student > Master | 22 | 12% |
Student > Bachelor | 18 | 10% |
Other | 11 | 6% |
Other | 15 | 8% |
Unknown | 27 | 15% |
Readers by discipline | Count | As % |
---|---|---|
Agricultural and Biological Sciences | 48 | 26% |
Immunology and Microbiology | 43 | 23% |
Medicine and Dentistry | 36 | 19% |
Biochemistry, Genetics and Molecular Biology | 18 | 10% |
Engineering | 2 | 1% |
Other | 7 | 4% |
Unknown | 32 | 17% |