ArticleFrontiers in immunology2013
Inhibitory Receptor Expression Depends More Dominantly on Differentiation and Activation than "Exhaustion" of Human CD8 T Cells.
Article in Frontiers in immunology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 152 papers, 1 of them a synthesis that pooled it.
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Who cites it
152 citing papers in PubMed, 1 synthesis or guideline pooled it, 244 citations in OpenAlex.
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- T Cell Transcriptomes from Paroxysmal Nocturnal Hemoglobinuria Patients Reveal Novel Signaling Pathways.Journal of immunology (Baltimore, Md. : 1950) · 2017Trial
- Sunitinib in patients with chemotherapy-refractory thymoma and thymic carcinoma: an open-label phase 2 trial.The Lancet. Oncology · 2015Trial
- Extracellular Vesicles as Master Regulators of Immune Modulation in Multiple Myeloma.International journal of molecular sciences · 2026Review
- Studying Macromolecular Composition in Cell-Cell Interfaces Using 3D Membrane Reconstitution Systems.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Expression of CD38 on resting peripheral iNKT cells defines an immature subpopulation with distinct functionality in humans.Immunology and cell biology · 2026Article
- How the wild things are: comparative T cell phenotyping and memory T cell identification in wild boar and domestic pigs.Frontiers in immunology · 2026Article
- cTfh Cell Activation and Changes in BTLA and LAG-3 Expression Differentially Associate With Poor Pregnancy Outcome in Plasmodium falciparum Placental Malaria.Journal of immunology research · 2026Article
- Association between T cell exhaustion and the recurrence of atrial fibrillation after cryoballoon ablation.Frontiers in immunology · 2026Article
- Composite score of PD-1Chinese journal of cancer research = Chung-kuo yen cheng yen chiu · 2025Article
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- Multi-compartment immune cell profiling highlights the prognostic relevance of CD127+ CD8+ T cells for patients with high-grade serous ovarian cancer.Frontiers in immunology · 2025Article
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- γδ T cells and the PD-1/PD-L1 axis: a love-hate relationship in the tumor microenvironment.Journal of translational medicine · 2024Review
- Vδ1 Effector and Vδ2 γδ T-Cell Subsets Shift in Frequency and Are Linked to Plasma Inflammatory Markers During Antiretroviral Therapy-Suppressed HIV Infection.The Journal of infectious diseases · 2024Article
- PD-1 knockout on cytotoxic primary murine CD8Frontiers in immunology · 2024Article
- Regulation of temporal cytokine production by co-stimulation receptors in TCR-T cells is lost in CAR-T cells.Immunotherapy advances · 2024Article
- Decoding NY-ESO-1 TCR T cells: transcriptomic insights reveal dual mechanisms of tumor targeting in a melanoma murine xenograft model.Frontiers in immunology · 2024Article
- Specific Polo-Like Kinase 1 Expression in Nodular Lymphocyte-Predominant Hodgkin Lymphoma Suggests an Intact Immune Surveillance Program.The American journal of pathology · 2024Article
92 more citing papers are in PubMed but not listed here.
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Authors and funding
5 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Under conditions of chronic antigen stimulation, such as persistent viral infection and cancer, CD8 T cells may diminish effector function, which has been termed "exhaustion." Expression of inhibitory Receptors (iRs) is often regarded as a hallmark of "exhaustion." Here we studied the expression of eight different iRs by CD8 T cells of healthy humans, including CTLA-4, PD1, TIM3, LAG3, 2B4, BTLA, CD160, and KLRG1. We show that many iRs are expressed upon activation, and with progressive differentiation to effector cells, even in absence of long-term ("chronic") antigenic stimulation. In particular, we evaluated the direct relationship between iR expression and functionality in CD8 T cells by using anti-CD3 and anti-CD28 stimulation to stimulate all cells and differentiation subsets. We observed a striking up-regulation of certain iRs following the cytokine production wave, in agreement with the notion that iRs function as a negative feedback mechanism. Intriguingly, we found no major impairment of cytokine production in cells positive for a broad array of iRs, as previously shown for PD1 in healthy donors. Rather, the expression of the various iRs strongly correlated with T cell differentiation or activation states, or both. Furthermore, we analyzed CD8 T cells from lymph nodes (LNs) of melanoma patients. Interestingly, we found altered iR expression and lower cytokine production by T cells from metastatic LNs, but also from non-metastatic LNs, likely due to mechanisms which are not related to exhaustion. Together, our data shows that expression of iRs per se does not mark dysfunctional cells, but is rather tightly linked to activation and differentiation. This study highlights the importance of considering the status of activation and differentiation for the study and the clinical monitoring of CD8 T cells.
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