Cell Interaction in B/W Mice: A Reversible Defect at the T-Cell Level

AbstractWhile numerous disease-modifying anti-rheumatic drugs (DMARDs) have brought about a dramatic paradigm shift in the management of rheumatoid arthritis (RA), unmet needs remain, such as the small proportion of patients who achieve drug-free status. The aim of this study was to explore key molecules for remission at the T cell level, which are known to be deeply involved in RA pathogenesis, and investigate the disease course of patients who achieved molecular remission (MR). We enrolled a total of 46 patients with RA and 10 healthy controls (HCs). We performed gene expression profiling and selected remission signature genes in CD4+ T cells and CD8+ T cells from patients with RA using machine learning methods. In addition, we investigated the benefits of achieving MR on disease control. We identified 9 and 23 genes that were associated with clinical remission in CD4+ and CD8+ T cells, respectively. Principal component analysis (PCA) demonstrated that their expression profiling was similar to those in HCs. For the remission signature genes in CD4+ T cells, the PCA result was reproduced using a validation cohort, indicating the robustness of these genes. A trend toward better disease control was observed during 12 months of follow-up in patients treated with tocilizumab in deep MR compared with those in non-deep MR, although the difference was not significant. The current study will promote our understanding of the molecular mechanisms necessary to achieve deep remission during the management of RA.

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PD-1 suppresses TCR-CD8 cooperativity during T-cell antigen recognition

Nature Communications ◽

10.1038/s41467-021-22965-9 ◽

2021 ◽

Vol 12 (1) ◽

Author(s):

Kaitao Li ◽

Zhou Yuan ◽

Jintian Lyu ◽

Eunseon Ahn ◽

Simon J. Davis ◽

...

Keyword(s):

T Cell ◽

T Cell Activation ◽

Cell Activation ◽

Clinical Success ◽

Clinical Intervention ◽

Cell Receptor ◽

Cell Interaction ◽

Antigen Recognition ◽

Inhibitory Function ◽

Src Homology

AbstractDespite the clinical success of blocking its interactions, how PD-1 inhibits T-cell activation is incompletely understood, as exemplified by its potency far exceeding what might be predicted from its affinity for PD-1 ligand-1 (PD-L1). This may be partially attributed to PD-1’s targeting the proximal signaling of the T-cell receptor (TCR) and co-stimulatory receptor CD28 via activating Src homology region 2 domain-containing phosphatases (SHPs). Here, we report PD-1 signaling regulates the initial TCR antigen recognition manifested in a smaller spreading area, fewer molecular bonds formed, and shorter bond lifetime of T cell interaction with peptide-major histocompatibility complex (pMHC) in the presence than absence of PD-L1 in a manner dependent on SHPs and Leukocyte C-terminal Src kinase. Our results identify a PD-1 inhibitory mechanism that disrupts the cooperative TCR–pMHC–CD8 trimolecular interaction, which prevents CD8 from augmenting antigen recognition, explaining PD-1’s potent inhibitory function and its value as a target for clinical intervention.

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Clinical characteristics and predictive value of lower CD4+T cell level in patients with moderate and severe COVID-19: a multicenter retrospective study

BMC Infectious Diseases ◽

10.1186/s12879-020-05741-w ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Xue-song Wen ◽

Dan Jiang ◽

Lei Gao ◽

Jian-zhong Zhou ◽

Jun Xiao ◽

...

Keyword(s):

Retrospective Study ◽

T Cell ◽

Lymphocyte Subsets ◽

Clinical Symptoms ◽

Independent Predictor ◽

Cd4 T Cell ◽

Hospital Death ◽

Consecutive Series ◽

Cell Level ◽

Global Pandemic

Abstract Background In December 2019, coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in Wuhan, Hubei, China. Moreover, it has become a global pandemic. This is of great value in describing the clinical symptoms of COVID-19 patients in detail and looking for markers which are significant to predict the prognosis of COVID-19 patients. Methods In this multicenter, retrospective study, 476 patients with COVID-19 were enrolled from a consecutive series. After screening, a total of 395 patients were included in this study. All-cause death was the primary endpoint. All patients were followed up from admission till discharge or death. Results The main symptoms observed in the study included fever on admission, cough, fatigue, and shortness of breath. The most common comorbidities were hypertension and diabetes mellitus. Patients with lower CD4+T cell level were older and more often male compared to those with higher CD4+T cell level. Reduced CD8+T cell level was an indicator of the severity of COVID-19. Both decreased CD4+T [HR:13.659; 95%CI: 3.235–57.671] and CD8+T [HR: 10.883; 95%CI: 3.277–36.145] cell levels were associated with in-hospital death in COVID-19 patients, but only the decrease of CD4+T cell level was an independent predictor of in-hospital death in COVID-19 patients. Conclusions Reductions in lymphocytes and lymphocyte subsets were common in COVID-19 patients, especially in severe cases of COVID-19. It was the CD8+T cell level, not the CD4+T cell level, that reflected the severity of the patient’s disease. Only reduced CD4+T cell level was independently associated with increased in-hospital death in COVID-19 patients. Trial registration Prognostic Factors of Patients With COVID-19, NCT04292964. Registered 03 March 2020. Retrospectively registered.

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