Association of HLA-DR, DQ Genotype With Different  -Cell Functions at IDDM Diagnosis in Japanese Children

Background Recently, it has been reported that Toll-like receptor 7 (TLR7) agonists can improve allergic rhinitis (AR) symptoms by up-regulation of Th1 cytokine release and suppression of Th2 cell functions. However, little is known of the expression of TLR7 in basophils of AR. Objective To explore the expression of TLR7 in basophils of AR, and influence of allergens on TLR7 expression. Methods The expression levels of TLR7 in basophils of patients with AR were determined by flow cytometry, and the influence of allergens on TLR7 expression was examined by real time (q) PCR. Results The percentages of TLR7+CCR3+ cells ( P < 0.001 and P = 0.011), TLR7+CD123+HLA-DR− cells ( P = 0 .016 and P = 0.042) and TLR7+CCR3+CD123+HLA-DR− cells ( P = 0.046 and P = 0.035) in blood granulocyte and mononucleated cell populations of the patients with AR were increased, respectively compared with HC subjects. TLR7 MFI on CCR3+ cells ( P = 0.050 and P = 0.043), CD123+HLA-DR− cells ( P < 0.001 and P = 0.002) and CCR3+CD123+HLA-DR− cells ( P < 0.001 and P = 0.003) were enhanced compared with HC subjects. Allergens Der p1 and OVA provoked upregulation of TLR7 expression at both protein and mRNA levels and IL-13 production in KU812 cells. House Dust Mite extract (HDME), Artemisia sieversiana wild allergen extract (ASWE), IL-31, IL-33, IL-37, and TSLP provoked elevation of IL-6 release from KU812 cells following 2 h incubation period. Conclusions The percentage of TLR7+ basophils and TLR7 expression intensity in a single basophil are both increased in the blood of patients with AR, indicating that basophils likely contribute to the pathogenesis of AR via TLR7.

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O13 HLA-DR, DQ genotype and heterogeneity of Japanese children with IDDM

Diabetes Research and Clinical Practice ◽

10.1016/s0168-8227(99)90013-x ◽

1999 ◽

Vol 44 ◽

pp. S6

Author(s):

Nobuo Matsuura ◽

Fumiyuki Yokota ◽

Koujika Zahari ◽

Mayumi Kazahari ◽

Nariyuki U. Oots ◽

...

Keyword(s):

Japanese Children ◽

Hla Dr

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Innate immune deficiencies in patients with COVID-19

10.1101/2021.03.29.21254560 ◽

2021 ◽

Author(s):

Marine Peyneau ◽

Vanessa Granger ◽

Paul-Henri Wicky ◽

Dounia Khelifi-Touhami ◽

Jean-François Timsit ◽

...

Keyword(s):

Innate Immunity ◽

Myeloid Cell ◽

Innate Immune ◽

Activation Markers ◽

Icu Patients ◽

Cell Functions ◽

Hla Dr ◽

Immune Deficiencies ◽

Severe Infections

AbstractCOVID-19 can cause acute respiratory distress syndrome (ARDS), leading to death in a significant number of individuals. Evidence of a strong role of the innate immune system is accumulating, but the precise cells and mechanism involved remain unclear. In this study, we investigated the links between circulating innate phagocyte phenotype and functions and severity in COVID-19 patients. Eighty-four consecutive patients were included, 44 of which were in intensive care units (ICU). We performed an in-depth phenotyping of neutrophil and monocyte subpopulations and measured soluble activation markers in plasma. Additionally, myeloid cell functions (phagocytosis, oxidative burst, and NETosis) were evaluated on fresh cells from patients. Resulting parameters were linked to disease severity and prognosis. Both ICU and non-ICU patients had circulating neutrophils and monocytes with an activated phenotype, as well as elevated concentrations of soluble activation markers (calprotectin, myeloperoxidase, neutrophil extracellular traps, MMP9, sCD14) in their plasma. ICU patients were characterized by increased CD10low CD13low immature neutrophils, LOX-1+ and CCR5+ immunosuppressive neutrophils, and HLA-DRlow CD14low downregulated monocytes. Markers of immature and immunosuppressive neutrophils were strongly associated with severity and poor outcome. Moreover, neutrophils and monocytes of ICU patients had impaired antimicrobial functions, which correlated with organ dysfunction, severe infections, and mortality. Our study reveals a marked dysregulation of innate immunity in COVID-19 patients, which was correlated with severity and prognosis. Together, our results strongly argue in favor of a pivotal role of innate immunity in COVID-19 severe infections and pleads for targeted therapeutic options.One Sentence SummaryOur study reveals a marked dysregulation of innate immunity in COVID-19 patients, which correlates with severity and prognosis.

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Characterization of a humanized IgG4 anti-HLA-DR monoclonal antibody that lacks effector cell functions but retains direct antilymphoma activity and increases the potency of rituximab

Blood ◽

10.1182/blood-2006-04-017921 ◽

2006 ◽

Vol 108 (8) ◽

pp. 2736-2744 ◽

Cited By ~ 42

Author(s):

Rhona Stein ◽

Zhengxing Qu ◽

Susan Chen ◽

David Solis ◽

Hans J. Hansen ◽

...

Keyword(s):

Monoclonal Antibody ◽

Effector Cell ◽

Cell Functions ◽

Hla Dr ◽

Complement Dependent Cytotoxicity ◽

Survival Pathway ◽

Anti Cd20

AbstractHLA-DR is under investigation as a target for monoclonal antibody (mAb) therapy of malignancies. Here we describe a humanized IgG4 form of the anti-HLA-DR mAb L243, hL243γ4P (IMMU-114), generated to provide an agent with selectivity toward neoplastic cells that can kill without complement-dependent cytotoxicity (CDC) or antibody-dependent cellular-cytotoxicity (ADCC), so as to reduce reliance on intact immunologic systems in the patient and effector mechanism-related toxicity. In vitro studies show that replacing the Fc region of hL243γ1, a humanized IgG1 anti-HLA-DR mAb, with the IgG4 isotype abrogates the effector cell functions of the antibody (ADCC and CDC) while retaining its antigen-binding properties, antiproliferative capacity (in vitro and in vivo), and the ability to induce apoptosis concurrent with activation of the AKT survival pathway. Growth inhibition was evaluated compared with and in combination with the anti-CD20 mAb rituximab, with the combination being more effective than rituximab alone in inhibiting proliferation. Thus, hL243γ4P is indistinguishable from hL243γ1 and the parental murine mAb in assays dependent on antigen recognition. The abrogation of ADCC and CDC, which are believed to play a major role in side effects of mAb therapy, may make this antibody an attractive clinical agent. In addition, combination of hL243γ4P with rituximab offers the prospect for improved patient outcome.

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Association of HLA-DR, -DQ Genotype and CTLA-4 Gene Polymorphism with Graves’ Disease in Japanese Children

Hormone Research in Paediatrics ◽

10.1159/000083137 ◽

2005 ◽

Vol 63 (2) ◽

pp. 55-60 ◽

Cited By ~ 6

Author(s):

Saika Iwama ◽

Ayako Ikezaki ◽

Noriko Kikuoka ◽

Hye-Sook Kim ◽

Hisafumi Matsuoka ◽

...

Keyword(s):

Gene Polymorphism ◽

Graves Disease ◽

Japanese Children ◽

Hla Dr

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Monoclonal antibody to a helper T-cell marker (Leu-3) blocks HLA-DR dependent T-cell functions

Human Immunology ◽

10.1016/0198-8859(82)90061-1 ◽

1982 ◽

Vol 5 (2) ◽

pp. 140-141

Author(s):

Claudia Benike ◽

Charles Metzler ◽

Paul Gatenby ◽

Robert Evans ◽

Edgar Engleman

Keyword(s):

Monoclonal Antibody ◽

T Cell ◽

Cell Marker ◽

Helper T Cell ◽

Cell Functions ◽

Hla Dr

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Flow Cytometric Analysis of T Cell Functions in CML Patients Under Imatinib Therapy

Blood ◽

10.1182/blood.v112.11.2633.2633 ◽

2008 ◽

Vol 112 (11) ◽

pp. 2633-2633

Author(s):

Deniz Goren Sahin ◽

Klara Dalva ◽

Sema Meric ◽

Gunhan Gurman ◽

Muhit Ozcan ◽

...

Keyword(s):

T Cells ◽

T Cell ◽

T Lymphocytes ◽

T Lymphocyte ◽

Cd4 Cells ◽

Cell Functions ◽

Control Subjects ◽

Group 4 ◽

Hla Dr ◽

Healthy Control

Abstract Imatinib is currently the most chosen agent in the treatment of CML patients. There are published articles reporting that imatinib has suppressive effects on T lymphocytes. However there is little information avaliable about the effects of imatinib on the immune regulation after allogeneic stem cell transplantation and effect of graft versus leukemia. In light of these observations, in our study, primary objective was in vivo analysis of T lymphocyte functions by flow cytometry and the secondary objective was to evaluate the possible functional changes that might occur under imatinib therapy in CML patients. A total of 29 patients and 9 healthy control subjects were enrolled in this cross sectional, clinical-laboratory study. CML patients were divided into three groups as newly diagnosed patients having no treatment (group 1), patients receiving imatinib for 1 year (group 2) and patients receiving imatinib more than 1 year (group 3), respectively. Healthy control subjects were regarded as group 4. To evaluate T lymphocyte functions, cells were induced by phorbol myristate acetate (PMA) and ionomisin then CD4+ T-cells were selected and IL-4 and IFN-γ expression on these cells; how much percentage of CD3+ T cells were activated (CD3+CD69+); CD8+ T lymphocytes and the ratio and grade of expression of HLA-ABC and HLA-DR on those cells were evaluated, respectively. In our study, there was no significant difference in terms of mean number of CD4+ cells between the groups (p=0.125). However, there was a tendency toward higher CD4+ cells in group 4. Cytokine expression analyses (IL-4 and IFNgamma) were found not to be statistically significant between the groups. (p values 0.112 and 0.165 respectively). It was striking that group 4 has lower IL-4 and IFNgamma expression values but just failed to reach a statistical significant level. On the other hand, mean number of CD4+ cells, which did not express IL-4 and IFNgamma, were statistically higher in group 4 when compared to other groups. There were no significant differences in terms of CD3+ cells and CD69+ expression, which was an early activation marker of T cells. However, it was found differences in % activation values (p=0.002) and % activation of subjects in group 4 was found to be decreased when compared to that of other groups (Figure 1). CD8+ cell ratio was found to be statistically lower in all CML patient groups when compared to that of healthy control subjects (p=0.001). The expression of HLA-ABC and HLA-DR on CD8+ cells was similar between the groups. We could not show any inhibitory effect of imatinib on T cell functions that could support clinical observations. It will be a research area how this interaction will be in new and more potent 2nd and 3rd generation tyrosine kinase inhibitors. Figure 1. Graph showing distribution of mean percent activity between the groups. Note that group 4 shows significant lower values of mean percent activity. Figure 1. Graph showing distribution of mean percent activity between the groups. Note that group 4 shows significant lower values of mean percent activity.

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Characterization of Dendritic Cell and Regulatory T Cell Functions againstMycobacterium tuberculosisInfection

BioMed Research International ◽

10.1155/2013/402827 ◽

2013 ◽

Vol 2013 ◽

pp. 1-14 ◽

Cited By ~ 13

Author(s):

Devin Morris ◽

Brenda Gonzalez ◽

Melissa Khurasany ◽

Christine Kassissa ◽

Jennifer Luong ◽

...

Keyword(s):

T Cells ◽

T Cell ◽

Antimycobacterial Activity ◽

Immune Functions ◽

Cellular Functions ◽

Cell Functions ◽

Hla Dr ◽

Microbial Infections ◽

Acquired Immune Responses ◽

Antigen Presenting

Glutathione (GSH) is a tripeptide that regulates intracellular redox and other vital aspects of cellular functions. GSH plays a major role in enhancing the immune system. Dendritic cells (DCs) are potent antigen presenting cells that participate in both innate and acquired immune responses against microbial infections. Regulatory T cells (Tregs) play a significant role in immune homeostasis. In this study, we investigated the effects of GSH in enhancing the innate and adaptive immune functions of DCs againstMycobacterium tuberculosis(M. tb) infection. We also characterized the functions of the sub-populations of CD4+T cells such as Tregs and non-Tregs in modulating the ability of monocytes to control the intracellularM. tbinfection. Our results indicate that GSH by its direct antimycobacterial activity inhibits the growth of intracellularM. tbinside DCs. GSH also increases the expressions of costimulatory molecules such as HLA-DR, CD80 and CD86 on the cell surface of DCs. Furthermore, GSH-enhanced DCs induced a higher level of T-cell proliferation. We also observed that enhancing the levels of GSH in Tregs resulted in downregulation in the levels of IL-10 and TGF-βand reduction in the fold growth ofM. tbinside monocytes. Our studies demonstrate novel regulatory mechanisms that favor both innate and adaptive control ofM. tbinfection.

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Upregulated Expression of Toll Like Receptor 7 in Peripheral Blood Basophils of Patients With Allergic Rhinitis

10.21203/rs.3.rs-51325/v1 ◽

2020 ◽

Author(s):

Lihong Wang ◽

Mengmeng Zhan ◽

Junling Wang ◽

Dong Chen ◽

Nan Zhao ◽

...

Keyword(s):

Allergic Rhinitis ◽

Trial Registration ◽

Mrna Levels ◽

Toll Like Receptor ◽

Clinical Trial Registration ◽

Cell Functions ◽

Hla Dr ◽

Ku812 Cells ◽

Registration Number ◽

Blood Granulocyte

Abstract Background: Recently, it has been reported that Toll-like receptor 7 (TLR7) agonists can improve allergic rhinitis (AR) symptoms by up-regulation of Th1 cytokine release and suppression of Th2 cell functions. However, little is known of the expression of TLR7 in basophils of AR.Objective: To explore the expression of TLR7 in basophils of AR, and influence of allergens on TLR7 expression.Methods: The expression levels of TLR7 in basophils of patients with AR were determined by flow cytometry, and the influence of allergens on TLR7 expression was examined by real time (q) PCR.Results: The percentages of TLR7+CCR3+ cells, TLR7+CD123+HLA-DR- cells and TLR7+CCR3+CD123+HLA-DR- cells in blood granulocyte and mononucleated cell populations of the patients with AR were increased, respectively compared with HC subjects. TLR7 MFI on CCR3+ cells, CD123+HLA-DR- cells and CCR3+CD123+HLA-DR- cells were enhanced. Allergens Der p1 and OVA provoked upregulation of TLR7 expression at both protein and mRNA levels and IL-13 production in KU812 cells. House Dust Mite extract (HDME), Artemisia sieversiana wild allergen extract (ASWE), IL-31, IL-33, IL-37, and TSLP provoked elevation of IL-6 release from KU812 cells following 2 h incubation period.Conclusions: The percentage of TLR7+ basophils and TLR7 expression intensity in a single basophil are both increased in the blood of patients with AR, indicating that basophils likely contribute to the pathogenesis of AR via TLR7. Trial Registration: Trial registry: Chinese clinical trial; registration number: ChiCTR-BOC-16010279.

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