Immunosuppressive Effect of Cordyceps CS-4 on Human Monocyte-Derived Dendritic Cellsin Vitro

Cordyceps CS-4 (C.CS-4), a vegetative form of Cordyceps that contains the same active compounds as the fruit body, is widely used as a substitute of Cordyceps in China. A number of studies have shown that Cordyceps can positively stimulate the activation of T lymphocytes, B lymphocytes, natural killer cells, and macrophages. In our previous study, we found that C.CS-4 could inhibit the proliferation of CD4+ T cells in autoimmune diseases and prevent the lymphocyte infiltration in tissues. However, it is still unclear how the lymphocytes are regulated by C.CS-4. In this study, we investigate the effect of C.CS-4 on human monocyte-derived dendritic cells ( Mo -DCs), which are generated from PBMCs by the treatment with GM-CSF and IL-4. It is observed that Mo -DCs pretreated with C.CS-4 show an immature phenotype. Moreover, C.CS-4 significantly inhibits proliferation of CD4+ T cells, attenuates the production of cytokines in Mo -DCs and balances the Th1 and Th2 response in immune system. Our findings indicate that C.CS-4 exerts the immunosuppressive effect through inhibiting the CD4+ T cells proliferation, regulating cytokine secretions of Th1 and Th2 response ( Mo -DCs) and inducing phenotypic immature of Mo -DCs which may be related to the antigen presenting dysfunction.

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SERPINB10 contributes to asthma by inhibiting the apoptosis of allergenic Th2 cells

Respiratory Research ◽

10.1186/s12931-021-01757-1 ◽

2021 ◽

Vol 22 (1) ◽

Author(s):

Yuqing Mo ◽

Ling Ye ◽

Hui Cai ◽

Guiping Zhu ◽

Jian Wang ◽

...

Keyword(s):

T Cells ◽

Allergic Asthma ◽

Cd4 T Cells ◽

Quantitative Polymerase Chain Reaction ◽

Allergic Inflammation ◽

Specific Ige ◽

Th2 Cells ◽

Th1 Cells ◽

Th2 Response ◽

Th1 And Th2

Abstract Background Serine peptidase inhibitor, clade B, member 10 (SERPINB10) contributes to allergic inflammation in asthma. However, its role in the T-helper type 2 (Th2) response of allergic asthma is not known. The goal of this study was to unveil the function of SERPINB10 in the Th2 response of allergic asthma and the mechanism by which SERPINB10 affects the viability of Th2 cells. Methods Th2 cytokines and serum levels of house dust mite (HDM)-specific IgE in bronchoalveolar lavage fluid were examined by ELISA in an HDM-induced asthma model. The number and apoptosis of Th1 and Th2 cells in mouse lungs were measured by flow cytometry. Naïve CD4 T cells from patients with asthma were cultured under appropriate polarizing conditions to generate Th1 and Th2 cells. SERPINB10 expression in polarized Th1 and Th2 cells was quantified by real-time reverse transcription-quantitative polymerase chain reaction. SERPINB10 expression was knocked down in human CD4 T cells with lentivirus. Results Knockdown of SERPINB10 expression significantly diminished HDM-induced Th2 cytokine secretion and level of HDM-specific IgE. After HDM exposure, SERPINB10-knockdown mice had diminished numbers of Th2 cells, but similar numbers of Th1 cells, compared with those in negative-control mice. Th2 cells of SERPINB10-knockdown mice were more susceptible to apoptosis than that of control mice. Stimulating T-cell receptors (TCRs) with anti-CD3 antibody caused upregulation of SERPINB10 expression in polarized Th2 cells, but not polarized Th1 cells. Knockdown of SERPINB10 expression resulted in fewer numbers and greater apoptosis of polarized Th2 cells. Conclusion Our results suggest that SERPINB10 may contribute to allergic inflammation and the Th2 response of asthma by inhibiting the apoptosis of Th2 cells.

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SERPINB10 Contributes to Asthma by Inhibiting the Apoptosis of Allergenic Th2 Cells

10.21203/rs.3.rs-135747/v1 ◽

2020 ◽

Author(s):

Yuqing Mo ◽

Ling Ye ◽

Hui Cai ◽

Guiping Zhu ◽

Jian Wang ◽

...

Keyword(s):

T Cells ◽

Allergic Asthma ◽

Cd4 T Cells ◽

Quantitative Polymerase Chain Reaction ◽

Allergic Inflammation ◽

Specific Ige ◽

Th2 Cells ◽

Th1 Cells ◽

Th2 Response ◽

Th1 And Th2

Abstract Background: Serine peptidase inhibitor, clade B, member 10 (SERPINB10) contributes to allergic inflammation in asthma. However, its role in the T-helper type 1 (Th1) /Th2 response of allergic asthma is not known. The goal of this study was to unveil the function of SERPINB10 in the Th2 response of allergic asthma and the mechanism by which SERPINB10 affects the viability of Th2 cells.Methods: Th2 cytokines and serum levels of house dust mite (HDM)-specific IgE in bronchoalveolar lavage fluid were examined by ELISA in an HDM-induced asthma model. The number and apoptosis of Th1 and Th2 cells in mouse lungs were measured by flow cytometry. Naïve CD4 T cells from patients with asthma were cultured under appropriate polarizing conditions to generate Th1 and Th2 cells. SERPINB10 expression in polarized Th1 and Th2 cells was quantified by real-time reverse transcription-quantitative polymerase chain reaction. SERPINB10 expression was knocked down in CD4 T cells with lentivirus. Results: Knockdown of SERPINB10 expression significantly diminished HDM-induced Th2 cytokine secretion and level of HDM-specific IgE. After HDM exposure, SERPINB10-knockdown mice had diminished numbers of Th2 cells, but similar numbers of Th1 cells, compared with those in negative-control mice. Th2 cells of SERPINB10-knockdown mice were more susceptible to apoptosis than that of control mice. Stimulating T-cell receptors (TCRs) with anti-CD3 antibody caused upregulation of SERPINB10 expression in polarized Th2 cells, but not polarized Th1 cells. Knockdown of SERPINB10 expression resulted in fewer numbers and greater apoptosis of polarized Th2 cells.Conclusion: Our results suggest that SERPINB10 may contributes to allergic inflammation and the Th2 response of asthma by inhibiting the apoptosis of Th2 cells.

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CCL19 and CCL21 Chemokines Induce Endocytosis and Augment Antigen Presentation in Human Mature Dendritic Cells.

Blood ◽

10.1182/blood.v104.11.2651.2651 ◽

2004 ◽

Vol 104 (11) ◽

pp. 2651-2651

Author(s):

Masahiro Ogasawara ◽

Junji Tanaka ◽

Masahiro Imamura ◽

Masaharu Kasai

Keyword(s):

T Cells ◽

Dendritic Cells ◽

Antigen Presentation ◽

Cd4 T Cells ◽

Leukemia Cell ◽

Human Monocyte ◽

Blood Monocytes ◽

Gm Csf ◽

Cell Lysate ◽

Cytokines And Chemokines

Abstract Dendritic cells (DCs) are potent antigen presenting cells capable of regulating immune responses. DCs lose the ability to capture and process antigens during maturation. In the present study, we examined the effects of CCR7 ligands, CCL19 and CCL21, on endocytosis and antigen presentation in human mature dendritic cells. Immature DCs were generated from peripheral blood monocytes by culturing with GM-CSF and IL4 for 2–3 days. For maturation, immature DCs were cultured with the addition of TNFα, IL1β, IL6 and prostaglandin E2 for another 24 hours. Immature or mature DCs were incubated with FITC-dextran with or without CCL19. Immature DCs internalized FITC-dextran efficiently independent of the presence of CCL19 after 1 hour incubation. On the other hand, mature DCs scarcely internalized FITC-dextran without CCL19. In the presence of CCL19, however, mature DCs internalized FITC-dextran significantly (approximately 60% positive). The effect of CCL19 on the uptake of FITC-dextran in mature DCs was dose and time dependent. CCL21 exerted a similar effect on mature DCs. Next, we examined whether CCL19 facilitates antigen presentation in mature dendritic cells. CD4+ T cells were cultured with irradiated autologous mature DCs which had been incubated with leukemia cell lysate with or without CCL19. Marked proliferation of CD4+ T cells occurred only when these cells were cultured with mature DCs loaded with leukemia cell lysate in the presence of CCL19. This is the first demonstration that chemokines have a pivotal role in endocytosis and antigen presentation by human monocyte-derived dendritic cells to the best of our knowledge. These results demonstrated that generation of potent antigen-loaded mature DCs in relatively short term culture using various cytokines and chemokines may have an important clinical implication to facilitate DC-based immunotherapy.

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Faculty Opinions recommendation of Cutting edge: primary B lymphocytes preferentially expand allogeneic FoxP3+ CD4 T cells.

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

10.3410/f.1091758.544396 ◽

2007 ◽

Author(s):

Andrea Sant

Keyword(s):

T Cells ◽

B Lymphocytes ◽

Cd4 T Cells ◽

Cutting Edge

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Graft-vs-leukemia activity and graft-vs-host disease induced by allogeneic Th1- and Th2-type CD4+ T cells in mice

The Hematology Journal ◽

10.1038/sj.thj.6200087 ◽

2001 ◽

Vol 2 (2) ◽

pp. 136-144 ◽

Cited By ~ 14

Author(s):

Matthias Zeis ◽

Lutz Uharek ◽

Götz Hartung ◽

Bertram Glass ◽

Jörg Steinmann ◽

...

Keyword(s):

T Cells ◽

Cd4 T Cells ◽

Host Disease ◽

Graft Vs Host Disease ◽

Th1 And Th2

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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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Macrophage-dependent Apoptosis of CD4+ T Lymphocytes from HIV-infected Individuals Is Mediated by FasL and Tumor Necrosis Factor

Journal of Experimental Medicine ◽

10.1084/jem.185.1.55 ◽

1997 ◽

Vol 185 (1) ◽

pp. 55-64 ◽

Cited By ~ 181

Author(s):

Andrew D. Badley ◽

David Dockrell ◽

Margaret Simpson ◽

Ron Schut ◽

David H. Lynch ◽

...

Keyword(s):

T Cells ◽

Tumor Necrosis Factor ◽

T Lymphocytes ◽

Cd4 T Cells ◽

Tumor Necrosis ◽

Human Macrophages ◽

Infected Cells ◽

Induced Apoptosis ◽

Antigen Presenting ◽

Necrosis Factor

Apoptosis of bystander uninfected CD4+ T lymphocytes by neighboring HIV-infected cells is observed in cell culture and in lymphoid tissue of HIV-infected individuals. This study addresses whether antigen-presenting cells such as human macrophages mediate apoptosis of CD4+ T cells from HIV-infected individuals. Uninfected human macrophages, and to a larger degree, HIV-infected macrophages mediate apoptosis of T cells from HIV-infected, but not from uninfected control individuals. This macrophage-dependent killing targets CD4+, but not CD8+ T lymphocytes from HIV-infected individuals, and direct contact between macrophages and lymphocytes is required. Additional analyses indicated that the apoptosis-inducing ligands, FasL and tumor necrosis factor (TNF), mediate this macrophage-induced apoptosis of CD4+ T cells. These results support a role for macrophage-associated FasL and TNF in the selective depletion of CD4+ T cells in HIV-infected individuals.

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Response of naive antigen-specific CD4+ T cells in vitro: characteristics and antigen-presenting cell requirements.

Journal of Experimental Medicine ◽

10.1084/jem.176.5.1431 ◽

1992 ◽

Vol 176 (5) ◽

pp. 1431-1437 ◽

Cited By ~ 156

Author(s):

M Croft ◽

D D Duncan ◽

S L Swain

Keyword(s):

T Cells ◽

Dendritic Cells ◽

T Cell ◽

Cd4 T Cells ◽

Cd4 Cells ◽

Peptide Antigen ◽

Naive T Cells ◽

Naïve T Cells ◽

Antigen Presenting

Because of the low frequency of T cells for any particular soluble protein antigen in unprimed animals, the requirements for naive T cell responses in specific antigens have not been clearly delineated and they have been difficult to study in vitro. We have taken advantage of mice transgenic for the V beta 3/V alpha 11 T cell receptor (TCR), which can recognize a peptide of cytochrome c presented by IEk. 85-90% of CD4+ T cells in these mice express the transgenic TCR, and we show that almost all such V beta 3/V alpha 11 receptor-positive cells have a phenotype characteristic of naive T cells, including expression of high levels of CD45RB, high levels of L-selectin (Mel-14), low levels of CD44 (Pgp-1), and secretion of interleukin 2 (IL-2) as the major cytokine. Naive T cells, separated on the basis of CD45RB high expression, gave vigorous responses (proliferation and IL-2 secretion) to peptide antigen presented in vitro by a mixed antigen-presenting cell population. At least 50% of the T cell population appeared to respond, as assessed by blast transformation, entry into G1, and expression of increased levels of CD44 by 24 h. Significant contributions to the response by contaminating memory CD4+ cells were ruled out by demonstrating that the majority of the CD45RB low, L-selectin low, CD44 high cells did not express the V beta 3/V alpha 11 TCR and responded poorly to antigen. We find that proliferation and IL-2 secretion of the naive CD4 cells is minimal when resting B cells present peptide antigen, and that both splenic and bone marrow-derived macrophages are weak stimulators. Naive T cells did respond well to high numbers of activated B cells. However, dendritic cells were the most potent stimulators of proliferation and IL-2 secretion at low cell numbers, and were far superior inducers of IL-2 at higher numbers. These studies establish that naive CD4 T cells can respond vigorously to soluble antigen and indicate that maximal stimulation can be achieved by presentation of antigen on dendritic cells. This model should prove very useful in further investigations of activation requirements and functional characteristics of naive helper T cells.

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Differentiation and stability of T helper 1 and 2 cells derived from naive human neonatal CD4+ T cells, analyzed at the single-cell level.

Journal of Experimental Medicine ◽

10.1084/jem.184.2.473 ◽

1996 ◽

Vol 184 (2) ◽

pp. 473-483 ◽

Cited By ~ 186

Author(s):

T Sornasse ◽

P V Larenas ◽

K A Davis ◽

J E de Vries ◽

H Yssel

Keyword(s):

T Cells ◽

Cell Differentiation ◽

Cd4 T Cells ◽

Biological Activities ◽

Th2 Cells ◽

Cell Phenotype ◽

T Helper ◽

Th1 Cell ◽

Th2 Cell ◽

Th1 And Th2

The development of CD4+ T helper (Th) type 1 and 2 cells is essential for the eradication of pathogens, but can also be responsible for various pathological disorders. Therefore, modulation of Th cell differentiation may have clinical utility in the treatment of human disease. Here, we show that interleukin (IL) 12 and IL-4 directly induce human neonatal CD4- T cells, activated via CD3 and CD28, to differentiate into Th1 and Th2 subsets. In contrast, IL-13, which shares many biological activities with IL-4, failed to induce T cell differentiation, consistent with the observation that human T cells do not express IL-13 receptors. Both the IL-12-induced Th1 subset and the IL-4-induced Th2 subset produce large quantities of IL-10, confirming that human IL-10 is not a typical human Th2 cytokine. Interestingly, IL-4-driven Th2 cell differentiation was completely prevented by an IL-4 mutant protein (IL-4.Y124D), indicating that this molecule acts as a strong IL-4 receptor antagonist. Analysis of single T cells producing interferon gamma or IL-4 revealed that induction of Th1 cell differentiation occurred rapidly and required only 4 d of priming of the neonatal CD4+ T cells in the presence of IL-12. The IL-12-induced Th1 cell phenotype was stable and was not significantly affected when repeatedly stimulated in the presence of recombinant IL-4. In contrast, the differentiation of Th2 cells occurred slowly and required not only 6 d of priming, but also additional restimulation of the primed CD4+ T cells in the presence of IL-4. Moreover, IL-4-induced Th2 cell phenotypes were not stable and could rapidly be reverted into a population predominantly containing Th0 and Th1 cells, after a single restimulation in the presence of IL-12. The observed differences in stability of IL-12- and IL-4-induced human Th1 and Th2 subsets, respectively, may have implications for cytokine-based therapies of chronic disease.

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