Primary Role of CD4+ T Cells and Supplemental Role of Mast Cells in Allergic Pulmonary Eosinophilia

T lymphocytes play a primary role in recovery from viral infections and in antiviral immunity. Although viral-specific CD8+ and CD4+ T cells have been shown to be able to lyse virally infected targets in vitro and promote recovery from lethal infection in vivo, the role of CD4+ T lymphocytes and their mechanism(s) of action in viral immunity are not well understood. The ability to further dissect the role that CD4+ T cells play in the immune response to a number of pathogens has been greatly enhanced by evidence for more extensive heterogeneity among the CD4+ T lymphocytes. To further examine the role of CD4+ T cells in the immune response to influenza infection, we have generated influenza virus-specific CD4+ T cell clones from influenza-primed BALB/c mice with differential cytokine secretion profiles that are defined as T helper type 1 (Th1) clones by the production of interleukin 2 (IL-2) and interferon gamma (IFN-gamma), or as Th2 clones by the production of IL-4, IL-5, and IL-10. Our studies have revealed that Th1 clones are cytolytic in vitro and protective against lethal challenge with virus in vivo, whereas Th2 clones are noncytolytic and not protective. Upon further evaluation of these clonal populations we have shown that not only are the Th2 clones nonprotective, but that pulmonary pathology is exacerbated as compared with control mice as evidenced by delayed viral clearance and massive pulmonary eosinophilia. These data suggest that virus-specific CD4+ T cells of the Th2 subset may not play a primary role in virus clearance and recovery and may lead to immune mediated potentiation of injury.

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Role of sensitized CD4+ T cells in the development and maintenance of pulmonary eosinophilia and allergic airway hyperresponsiveness (AHR) following primary and secondary airway challenge

Journal of Allergy and Clinical Immunology ◽

10.1016/s0091-6749(03)81102-8 ◽

2003 ◽

Vol 111 (2) ◽

pp. S305

Author(s):

A. Joetham ◽

C. Taube ◽

Z. Cui ◽

K. Takeda ◽

E.W. Gelfand

Keyword(s):

T Cells ◽

Cd4 T Cells ◽

Airway Hyperresponsiveness ◽

Pulmonary Eosinophilia

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The Expression of IL-17, in Chronic Spontaneous Urticaria Is Linked to Semaphorin5A

Biomolecules ◽

10.3390/biom11030373 ◽

2021 ◽

Vol 11 (3) ◽

pp. 373

Author(s):

Matanis Lobna ◽

Eiza Nasren ◽

Sabag Adi ◽

Bejar Jacob ◽

Gimenez-Arnau Ana Maria ◽

...

Keyword(s):

T Cells ◽

Mast Cells ◽

Cd4 T Cells ◽

Autoimmune Disorder ◽

Chronic Spontaneous Urticaria ◽

Healthy Controls ◽

Peripheral T Cells ◽

Healthy Control ◽

Control Skin

Background: Patients with chronic spontaneous urticaria (CSU), an autoimmune disorder, show increased skin expression of IL-17A and can benefit from treatment with the anti-IL-17A biologic secukinumab. The mechanisms that drive IL-17A expression in CSU are currently unknown, but may involve Semaphorin5A (Sema5A). Objective: To explore the expression, role, and effects of Sema5A in CSU and its link to IL-17A. Material and Methods: We investigated patients with CSU and healthy controls for skin expression of expressing peripheral T cells. Results: Sema5A was highly expressed in the skin of CSU patients as compared to healthy control skin. Both CD4+ T cells and mast cells in CSU skin expressed Sema5A, and many of them expressed both Sema5A and IL-17A. Patients with CSU had significantly higher rates of IL-17A-expressing CD4+ T cells as compared to healthy controls. Incubation with Sema5A increased the rates of IL-17A-expressing CD4+ T cells in healthy controls to CSU levels. Conclusion: Sema5A may drive the expression and effects of IL-17A in CSU. Further studies in larger cohorts are needed to confirm the role of Sema5A in the pathogenesis of CSU and to explore its potential as a therapeutic target.

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The role of CTLA-4 during the activation of resting CD4+ T-cells

Immunology Letters ◽

10.1016/s0165-2478(97)87051-4 ◽

1997 ◽

Vol 56 (1-3) ◽

pp. 56-57

Author(s):

M Brunner

Keyword(s):

T Cells ◽

Cd4 T Cells

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The role of CCR2+ CD4 T cells in lung fibrosis

Pneumologie ◽

10.1055/s-0034-1367779 ◽

2014 ◽

Vol 68 (S 01) ◽

Author(s):

K Milger ◽

Y Yu ◽

E Brudy ◽

M Irmler ◽

A Skapenko ◽

...

Keyword(s):

T Cells ◽

Cd4 T Cells ◽

Lung Fibrosis

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Faculty Opinions recommendation of A crucial role of CD4 T cells as a functional source of CD154 in the initiation of insulin-dependent diabetes mellitus in the non-obese diabetic mouse.

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

10.3410/f.1012620.186383 ◽

2003 ◽

Author(s):

Matthias von Herrath

Keyword(s):

Diabetes Mellitus ◽

T Cells ◽

Crucial Role ◽

Cd4 T Cells ◽

Insulin Dependent Diabetes Mellitus ◽

Diabetic Mouse ◽

Insulin Dependent Diabetes ◽

Dependent Diabetes Mellitus ◽

Insulin Dependent

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Ceramide Synthase 2 Null Mice Are Protected from Ovalbumin-Induced Asthma with Higher T Cell Receptor Signal Strength in CD4+ T Cells

International Journal of Molecular Sciences ◽

10.3390/ijms22052713 ◽

2021 ◽

Vol 22 (5) ◽

pp. 2713

Author(s):

Sun-Hye Shin ◽

Kyung-Ah Cho ◽

Hee-Soo Yoon ◽

So-Yeon Kim ◽

Hee-Yeon Kim ◽

...

Keyword(s):

T Cells ◽

T Cell ◽

T Cell Receptor ◽

Cd4 T Cells ◽

Acyl Chain ◽

Signal Strength ◽

Cell Receptor ◽

Ceramide Synthase ◽

Asthmatic Patients

(1) Background: six mammalian ceramide synthases (CerS1–6) determine the acyl chain length of sphingolipids (SLs). Although ceramide levels are increased in murine allergic asthma models and in asthmatic patients, the precise role of SLs with specific chain lengths is still unclear. The role of CerS2, which mainly synthesizes C22–C24 ceramides, was investigated in immune responses elicited by airway inflammation using CerS2 null mice. (2) Methods: asthma was induced in wild type (WT) and CerS2 null mice with ovalbumin (OVA), and inflammatory cytokines and CD4 (cluster of differentiation 4)+ T helper (Th) cell profiles were analyzed. We also compared the functional capacity of CD4+ T cells isolated from WT and CerS2 null mice. (3) Results: CerS2 null mice exhibited milder symptoms and lower Th2 responses than WT mice after OVA exposure. CerS2 null CD4+ T cells showed impaired Th2 and increased Th17 responses with concomitant higher T cell receptor (TCR) signal strength after TCR stimulation. Notably, increased Th17 responses of CerS2 null CD4+ T cells appeared only in TCR-mediated, but not in TCR-independent, treatment. (4) Conclusions: altered Th2/Th17 immune response with higher TCR signal strength was observed in CerS2 null CD4+ T cells upon TCR stimulation. CerS2 and very-long chain SLs may be therapeutic targets for Th2-related diseases such as asthma.

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Aging diminishes the resistance of AO rats to EAE: putative role of enhanced generation of GM-CSF Expressing CD4+ T cells in aged rats

Immunity & Ageing ◽

10.1186/s12979-015-0044-x ◽

2015 ◽

Vol 12 (1) ◽

Cited By ~ 8

Author(s):

Zorica Stojić-Vukanić ◽

Mirjana Nacka-Aleksić ◽

Ivan Pilipović ◽

Ivana Vujnović ◽

Veljko Blagojević ◽

...

Keyword(s):

T Cells ◽

Cd4 T Cells ◽

Aged Rats ◽

Gm Csf ◽

Putative Role

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Human Mucosal Mast Cells Capture HIV-1 and Mediate Viraltrans-Infection of CD4+T Cells

Journal of Virology ◽

10.1128/jvi.03008-15 ◽

2015 ◽

Vol 90 (6) ◽

pp. 2928-2937 ◽

Cited By ~ 16

Author(s):

Ai-Ping Jiang ◽

Jin-Feng Jiang ◽

Ji-Fu Wei ◽

Ming-Gao Guo ◽

Yan Qin ◽

...

Keyword(s):

T Cells ◽

Mast Cells ◽

Cell Surface ◽

Bacterial Infections ◽

Mucosal Mast Cells ◽

Mucosal Tissues ◽

Viral Particles ◽

Molecular Patterns ◽

Hiv 1

ABSTRACTThe gastrointestinal mucosa is the primary site where human immunodeficiency virus type 1 (HIV-1) invades, amplifies, and becomes persistently established, and cell-to-cell transmission of HIV-1 plays a pivotal role in mucosal viral dissemination. Mast cells are widely distributed in the gastrointestinal tract and are early targets for invasive pathogens, and they have been shown to have increased density in the genital mucosa in HIV-infected women. Intestinal mast cells express numerous pathogen-associated molecular patterns (PAMPs) and have been shown to combat various viral, parasitic, and bacterial infections. However, the role of mast cells in HIV-1 infection is poorly defined. In this study, we investigated their potential contributions to HIV-1 transmission. Mast cells isolated from gut mucosal tissues were found to express a variety of HIV-1 attachment factors (HAFs), such as DC-SIGN, heparan sulfate proteoglycan (HSPG), and α4β7 integrin, which mediate capture of HIV-1 on the cell surface. Intriguingly, following coculture with CD4+T cells, mast cell surface-bound viruses were efficiently transferred to target T cells. Prior blocking with anti-HAF antibody or mannan before coculture impaired viraltrans-infection. Cell-cell conjunctions formed between mast cells and T cells, to which viral particles were recruited, and these were required for efficient cell-to-cell HIV-1 transmission. Our results reveal a potential function of gut mucosal mast cells in HIV-1 dissemination in tissues. Strategies aimed at preventing viral capture and transfer mediated by mast cells could be beneficial in combating primary HIV-1 infection.IMPORTANCEIn this study, we demonstrate the role of human mast cells isolated from mucosal tissues in mediating HIV-1trans-infection of CD4+T cells. This finding facilitates our understanding of HIV-1 mucosal infection and will benefit the development of strategies to combat primary HIV-1 dissemination.

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