Healthy immune response to allergens: T regulatory cells and more

2006 ◽  
Vol 18 (6) ◽  
pp. 738-744 ◽  
Author(s):  
Mübeccel Akdis
Keyword(s):  
Immune Response ◽  
T Regulatory Cells ◽  
Regulatory Cells

Abstract 13073: Epicardial YAP/TAZ Regulate an Immune Suppressive Response Following Myocardial Infarction

Circulation ◽  
2015 ◽  
Vol 132 (suppl_3) ◽  
Author(s):  
Vimal Ramjee ◽  
Manvendra K Singh ◽  
Feiyan Liu ◽  
Kurt A Engleka ◽  
Lauren J Manderfield ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Immune Response ◽  
T Cells ◽  
Heart Disease ◽  
T Regulatory Cells ◽  
Hippo Signaling ◽  
Regulatory Cells ◽  
Strong Immune Response ◽  
Inflammation Response ◽  
Injured Myocardium

Ischemic heart disease constitutes the most prevalent type of heart disease in the US. Remodeling post-myocardial infarction (MI) is a multifaceted process driven by a strong immune response. Regulatory T-cells, a subset of CD4+ T-cells, have been shown to suppress the innate and adaptive immune response following myocardial injury to allow for less deleterious remodeling. To date, the precise mechanism by which injured myocardium recruits these suppressive immune cells remains unknown. Here, we show a novel role for the epicardium in suppressing the post-infarct inflammation response through recruitment of T-regulatory cells. The Hippo pathway is a signal transduction pathway, which has gained importance in determining organ size and is implicated as a critical regulator of tissue regeneration. Mice deficient in epicardial YAP/TAZ, two core effectors of the Hippo signaling pathway, develop profound pericardial inflammation, thoracic adhesions and myocardial fibrosis post-MI, with resultant cardiomyopathy and death. These mice demonstrate fewer suppressive T-regulatory cells in the injured myocardium, due to a deficiency of interferon-gamma, a known inducer of these T-cells. Collectively, these results suggest a novel role for Hippo signaling in immune regulation. In addition, our data suggest that the epicardium plays an important role in homing suppressive T-regulatory cells to injured myocardium so that the inflammation response may be attenuated following MI.

Unraveling the immune response during AIHA

Blood ◽  
2008 ◽  
Vol 111 (2) ◽  
pp. 483-483
Author(s):  
Neil D. Avent
Keyword(s):  
Immune Response ◽  
Autoimmune Disease ◽  
Hemolytic Anemia ◽  
Autoimmune Hemolytic Anemia ◽  
T Regulatory Cells ◽  
Regulatory Cells

In this issue of Blood, Ward and colleagues make some novel fundamental observations on the nature of the immune response during autoimmune hemolytic anemia (AIHA). They show a key role for T regulatory cells (Tregs) in the pathogenesis of this autoimmune disease.

scholarly journals Increased T regulatory cells lead to development of Th2 immune response in male SJL mice

Autoimmunity ◽  
2010 ◽  
Vol 44 (3) ◽  
pp. 219-228 ◽  
Author(s):  
Shabbir Hussain ◽  
Stefanie J. Kirwin ◽  
Stephen A. Stohlman
Keyword(s):  
Immune Response ◽  
T Regulatory Cells ◽  
Regulatory Cells ◽  
Th2 Immune Response

scholarly journals Deregulation of the immune system in patients with chronic lymphocytic leukemia

2019 ◽  
Vol 73 ◽  
pp. 117-132
Author(s):  
Katarzyna Skórka ◽  
Marlena Kot ◽  
Joanna Knap ◽  
Krzysztof Giannopoulos
Keyword(s):  
Immune Response ◽  
Immune System ◽  
Chronic Lymphocytic Leukemia ◽  
T Regulatory Cells ◽  
Suppressor Cells ◽  
Pure Red Cell Aplasia ◽  
Lymphocytic Leukemia ◽  
Regulatory Cells ◽  
Autoimmune Processes ◽  
Autoimmune Cytopenias

Chronic lymphocytic leukemia (CLL) constitutes the most common leukemia in adults living in western countries. The clinical course of the disease is extremely heterogeneous and pathogenesis is still unknown. Immune system disorders in CLL patients are observed in the early stages of the disease and worsen during clinical observation. On the one hand, CLL patients are characterized by immunosupresion and on the other hand, autoimmune processes. The immunosuppression observed in patients with CLL is associated with disorders of non‑specific immune response as well as T‑cell and B‑cell response, leading to frequent and severe infections. The immune system of patients with CLL could be also inhibited by many immunosuppressive factors occurred in tumor microenvironment, including populations of immune cells, which include myeloid‑derived suppressor cells (MDSCs), T regulatory cells (Treg) and the newly described B regulatory cells (Breg). It was shown that CLL cells can regulate immune response and escape from the surveillance of the immune system through the PD‑1/PD‑L signalling pathway. Interestingly, reduced immune response in CLL patients may be accompanied by autoimmune processes clinically manifested as autoimmune cytopenias. The secondary autoimmune cytopenias complicating the course of the disease include autoimmune hemolytic anemia (AIHA), immune thrombocytopenia purpura (ITP), pure red cell aplasia (PRCA) and autoimmune granulocytopenia (AG). Identification of immunological disorders in patients with CLL is necessary to understand the biology of the disease and to select appropriate treatment patterns based on modulation of the immune system.

scholarly journals CD4 Lymphocytes and T Regulatory Cells Show Distinct Phenotypes in Follicular Lymphoma and Classical Hodgkin Lymphoma Which May Account for Differences in Responses to Checkpoint Therapy

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 1513-1513
Author(s):  
Sary El Daker ◽  
Qi Gao ◽  
Mikhail Roshal ◽  
Ahmet Dogan
Keyword(s):  
Immune Response ◽  
T Cells ◽  
Lymph Node ◽  
Tumor Microenvironment ◽  
T Regulatory Cells ◽  
Proliferation Index ◽  
Classical Hodgkin Lymphoma ◽  
Regulatory Cells ◽  
Treg Subset ◽  
Provision Of Services

Physiologically T-regulatory cells (Treg) suppress immune responses against self-antigens preventing autoimmunity. However, in cancer they are believed to suppress anti-tumor immune response, and the presence of Treg in the tumor microenvironment has been associated with adverse outcome in most cancers. Treg are integral part of tumor microenvironment in lymphoma, and can use different mechanisms to inhibit both adaptive and immune response (including CD4, CD8, DC, macrophages, B-cells and NK cells) modulating therefore the interaction between lymphoma and the host microenvironment. Increased numbers of Treg have been associated with adverse clinical outcome in follicular lymphoma (FL) but a more favorable outcome in classical Hodgkin lymphoma (CHL). In this study we examined Treg phenotype in detail using multiparameter flow cytometry in lymph node specimens with normal histology (NLN) and involved by FL and CHL. We report that both CD4 positive T-cells and Treg subset show distinct phenotypes in different disease entities suggesting different biological functions. Single cell suspensions were prepared from NLN (n=10) and lymph node biopsies involved by FL (n=10) and CHL (n=10), and high dimensional multiparameter flow cytometric immunophenotyping was performed using antibodies against immune checkpoints (TIGIT, TIM3, PD-1, CD96, LAG3, CTLA4, CD73). To characterize the CD4 T-cell compartments we used a dimensionality reduction algorithm for non-linear data representations (tSNE). We studied the CD4+FoxP3-CD25- and Treg characterized by CD4+FoxP3+CD25+ phenotype separately and in both the compartments we identified and characterized subpopulations specific for each of the disease cohorts. tSNE representations CD4 positive T-cells and Treg showed different distributions in NLN, FL and HL. In NLN, CD4 cells broader heterogeneity without distinct clusters whereas in FL and CHL CD4 positive T-cells and Treg (Figure 2 A-B) showed highly polarized phenotypes which were distinct from each other and nearly absent within normal Treg compartment. We observed a strong expression of the immune checkpoint regulators TIM3, LAG3, CTL4, Tbet and PD1 in CD4 T-cells derived from HL tissues. In contrast FL CD4 T-cells were mainly characterized by an up regulation of PD1, CTLA4 and TIGIT. The TIGIT+ cells in FL samples are mainly CXCR5+PD1bright and they up regulate CTLA-4 in the FoxP3+ compartment. In all the neoplastic tissues the FoxP3+CD25+ T-Reg express mainly an activated/memory phenotype (CD45RO+CTLA4+), but while in HL microenvironment they show a TH1 phenotype (CXCR3+Tbet+), in FL they mainly express PD1+CXCR5+ (Figure 1B). Additionally, the dominant population of regulatory T-cells derived from HL samples down modulate PD1 expression, show high level of expression of TH1-associated transcription factor Tbet and have high proliferation index, while in FL, PD1 is brightly expressed, Tbet is not expressed and proliferation index is low in the dominant population (Figure 1A). The distinct phenotypic differences of Treg in FL lymphoma and CHL may account for the better prognosis seen in CHL with increased Treg which has TH1 like phenotype, therefore predicted to have anti-tumor activity. The differences seen in the expression immune checkpoint regulators both on CD4 positive T-cells and Treg subset may explain different rate responses seen in FL compared to CHL with checkpoint therapy. Disclosures Roshal: Physicians' Education Resource: Other: Provision of services; Celgene: Other: Provision of Services; Auron Therapeutics: Equity Ownership, Other: Provision of services. Dogan:Corvus Pharmaceuticals: Consultancy; Novartis: Consultancy; Takeda: Consultancy; Roche: Consultancy, Research Funding; Celgene: Consultancy; Seattle Genetics: Consultancy.

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