AB0346 THE NUMERAL CHANGES OF PERIPHERAL LYMPHOCYTE SUBSETS IN PATIENTS WITH RHEUMATOID ATHRITIS AND THEIR RESTORATIONS AFTER RECEIVED COMBINED IMMUNOMODULATORY THERAPY

Background:Rheumatoid arthritis (RA) is an aggressive immune-mediated joint disease with synovial inflammation and joint destruction characterized by abnormal immune responses to self-antigens1. An imbalance in pro- and anti-inflammatory lymphocyte subsets has been considered to contribute to the pathogenesis of RA2. However, the detailed lymphocyte statuses of RA patients are required clarified and the effect of immunomodulatory therapy on the lymphocyte subsets is unclear3.Objectives:To investigate the status of lymphocyte subsets in peripheral blood (PB) of RA patients at relatively large-sample size and the changes of them after our immune regulatory combination treatment.Methods:This cross-sectional study enrolled 3016 patients with RA who met the ACR’s revised RA diagnostic classification in 1987 as well as 206 healthy controls (HCs). Among these participations, 1415 patients have received the treatment of immunomodulatory drugs (IMiDs) such as low-dose interleukin-2, rapamycin, metformin, retinoic acid etc. Flow cytometry (FCM) was used to measure the levels of PB lymphocyte subgroups and CD4+T subsets in RA patients before and after the treatments and HCs. Data were expressed as mean ± standard deviation to the distribution. Independent-samples T test and paired-samples T test were applied.Pvalue <0.05 were considered statistically significant.Results:Compared with HCs, patients with RA had a lower absolute numbers of total T, CD8+T, NK and Tregs (P<0.05), decreased percentages of NK, Th1, Th2 and Th17 (P<0.05), but higher ratios of Teffs/Tregs such as Th1/Tregs and Th17/Tregs (P<0.05), indicating a disturbance of immune systems (Figure 1). After receiving combined immunomodulatory therapy, the absolute numbers of T, B, CD4+T, CD8+T, NK, Th1, Th17 and Tregs were dramatically increased (P<0.05) and the percentages of B, Th1, CD4+T and Tregs were also increased (P<0.05). Although these subsets increased globally, the ratio of Teffs/Tregs such as Th2/Tregs and Th17/Tregs tended to decrease, suggesting a rebalance of immune systems(Figure 2).Conclusion:Impaired peripheral lymphocytes especially insufficiency of Tregs might played an important role in pathogenesis of RA. Immunoregulatory combination therapies could promote the proliferation and functional recovery of Tregs in patients and help to alleviate disease activity.References:[1]Smolen JS, Aletaha D, McInnes IB. Rheumatoid arthritis. (1474-547X (Electronic))[2]Kondo Y, Yokosawa M, Kaneko S, et al. Review: Transcriptional Regulation of CD4+ T Cell Differentiation in Experimentally Induced Arthritis and Rheumatoid Arthritis. (2326-5205 (Electronic))[3]Fonseka CY, Rao DA, Raychaudhuri S. Leveraging blood and tissue CD4+ T cell heterogeneity at the single cell level to identify mechanisms of disease in rheumatoid arthritis. (1879-0372 (Electronic))Acknowledgments:None.Disclosure of Interests:None declared

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Faculty Opinions recommendation of Kynurenine Reduces Memory CD4 T-Cell Survival by Interfering with Interleukin-2 Signaling Early during HIV-1 Infection.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.726472546.793524045 ◽

2016 ◽

Author(s):

Jay Rappaport

Keyword(s):

T Cell ◽

Cell Survival ◽

Interleukin 2 ◽

Cd4 T Cell ◽

T Cell Survival ◽

Hiv 1

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Lymphocyte subset analysis to evaluate the prognosis of HIV-negative patients with pneumocystis pneumonia

BMC Infectious Diseases ◽

10.1186/s12879-021-06124-5 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Fan Jin ◽

Jing Xie ◽

Huan-ling Wang

Keyword(s):

T Cell ◽

Cell Count ◽

Lymphocyte Subsets ◽

Nk Cell ◽

Cd8 T Cell ◽

Pneumocystis Pneumonia ◽

Lymphocyte Subset ◽

Cd4 T Cell ◽

Cell Counts ◽

Hiv Negative

Abstract Objectives We analysed the peripheral blood lymphocyte subsets of human immunodeficiency virus (HIV)-negative patients infected with pneumocystis pneumonia (PCP) to determine the relationships between the levels of different types of lymphocytes and the prognosis of patients. Methods We retrospectively reviewed HIV-negative patients with PCP diagnosed in our department. All the eligible patients underwent lymphocyte subset analysis on admission. Results A total of 88 HIV-negative PCP patients were enrolled in the study. In univariate analyses, low CD4+ T cell count, low CD8+ T cell count, and low natural killer cell (NK cell) count were associated with higher in-hospital mortality. CD8+ T cell count ≤300/μL was found to be an independent risk factor for poor prognosis in multivariate logistical regression analysis (p = 0.015, OR = 11.526, 95% CI = 1.597–83.158). Although low CD4+ T cell and NK cell counts were not independent risk factors, the mortality rates of PCP patients decreased as the CD4+ T cell and NK cell counts increased. Conclusion The immune process of Pneumocystis jirovecii infection is complex but important. We propose that lymphocyte subsets could give clinicians a better understanding of patient immune status, helping with the early identification of potentially lethal infections and treatment decision making, such as adjusting the immunosuppressive regimen and choosing an appropriate patient monitoring level.

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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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A gene module associated with dysregulated TCR signaling pathways in CD4 + T cell subsets in rheumatoid arthritis

Journal of Autoimmunity ◽

10.1016/j.jaut.2017.11.001 ◽

2018 ◽

Vol 89 ◽

pp. 21-29 ◽

Cited By ~ 12

Author(s):

Shuji Sumitomo ◽

Yasuo Nagafuchi ◽

Yumi Tsuchida ◽

Haruka Tsuchiya ◽

Mineto Ota ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

T Cell ◽

Signaling Pathways ◽

T Cell Subsets ◽

Cd4 T Cell ◽

Gene Module ◽

Tcr Signaling

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CD4 T Cell Survival after Intermittent Interleukin‐2 Therapy Is Predictive of an Increase in the CD4 T Cell Count of HIV‐Infected Patients

The Journal of Infectious Diseases ◽

10.1086/591250 ◽

2008 ◽

Vol 198 (6) ◽

pp. 843-850 ◽

Cited By ~ 15

Author(s):

Sarah W. Read ◽

Richard A. Lempicki ◽

Michele Di Mascio ◽

Sharat Srinivasula ◽

Rosanne Burke ◽

...

Keyword(s):

T Cell ◽

Cell Survival ◽

Cell Count ◽

Interleukin 2 ◽

Cd4 T Cell ◽

T Cell Survival ◽

Cd4 T Cell Count

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Clinical characteristics and predictive value of low CD4+T cell count in patients with moderate and severe COVID-19: A multicenter retrospective study

10.21203/rs.3.rs-46009/v2 ◽

2020 ◽

Author(s):

Xue-song Wen ◽

Lei Gao ◽

Dan Jiang ◽

Xiao-cheng Cheng ◽

Bin He ◽

...

Keyword(s):

Retrospective Study ◽

T Cell ◽

Lymphocyte Subsets ◽

Clinical Symptoms ◽

Independent Predictor ◽

Cd4 T Cell ◽

Hospital Death ◽

Consecutive Series ◽

Global Pandemic ◽

Cd4 T Cell Count

Abstract BackgroundIn December 2019, coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in Wuhan, Hubei, China. And, it has become a global pandemic. Describe the patient's clinical symptoms in detail, finding markers that predict the prognosis of patients with COVID-19 are of great value.MethodsIn this multicenter, retrospective study, 476 patients with COVID-19 were recruited 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.ResultsThe dominant symptoms observed in the study included fever on admission, cough, fatigue, and shortness of breath. The most frequent comorbidities were hypertension and diabetes. Compared with patients with higher CD4+T cell levels, patients with lower CD4+T cell levels were older and were more frequently male. Reduction of CD8+T cell is an indicator of the severity of COVID-19. Both decreased CD4+T cell [HR:13.659; 95%CI: 3.235-57.671] and CD8+T cell [HR: 10.883; 95%CI: 3.277-36.145] were associated with in-hospital death in COVID-19 patients, but only decreased CD4+T cell was an independent predictor of in-hospital death in COVID-19 patients.ConclusionsReductions in lymphocytes and lymphocyte subsets were common in COVID-19 patients, especially in severe cases. It was the CD8+T cell, not the CD4+T cell, that reflected the severity of the patient’s disease. Only CD4+T cell reduction 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. https://clinicaltrials.gov/ct2/show/NCT04292964.

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IL-2 coordinates IL-2–producing and regulatory T cell interplay

Journal of Experimental Medicine ◽

10.1084/jem.20122759 ◽

2013 ◽

Vol 210 (12) ◽

pp. 2707-2720 ◽

Cited By ~ 56

Author(s):

Inês F. Amado ◽

Julien Berges ◽

Rita J. Luther ◽

Marie-Pierre Mailhé ◽

Sylvie Garcia ◽

...

Keyword(s):

T Cell ◽

Quorum Sensing ◽

Interleukin 2 ◽

Cell Subset ◽

Cd4 T Cell ◽

Cell Numbers ◽

Regulatory Circuit ◽

Reporter Mice ◽

Lymphocyte Homeostasis

Many species of bacteria use quorum sensing to sense the amount of secreted metabolites and to adapt their growth according to their population density. We asked whether similar mechanisms would operate in lymphocyte homeostasis. We investigated the regulation of the size of interleukin-2 (IL-2)–producing CD4+ T cell (IL-2p) pool using different IL-2 reporter mice. We found that in the absence of either IL-2 or regulatory CD4+ T (T reg) cells, the number of IL-2p cells increases. Administration of IL-2 decreases the number of cells of the IL-2p cell subset and, pertinently, abrogates their ability to produce IL-2 upon in vivo cognate stimulation, while increasing T reg cell numbers. We propose that control of the IL-2p cell numbers occurs via a quorum sensing–like feedback loop where the produced IL-2 is sensed by both the activated CD4+ T cell pool and by T reg cells, which reciprocally regulate cells of the IL-2p cell subset. In conclusion, IL-2 acts as a self-regulatory circuit integrating the homeostasis of activated and T reg cells as CD4+ T cells restrain their growth by monitoring IL-2 levels, thereby preventing uncontrolled responses and autoimmunity.

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