Reduced IL-4 and interferon-gamma (IFN-γ) expression by CD4 T cells in patients with chronic lymphocytic leukaemia

BMP4 is a key growth factor well known in promoting bone regeneration and has been reported to be able to regulate T cell development in the thymus. Here, we showed that BMP4 downregulates the activation of naïve CD4+ T cells and the IFN-γ production of CD4+ T cells without increasing regulatory T cells. BMP4 could also moderate glycolysis of T cells and regulate Hif1α expression. Furthermore, BMP4 showed a suppressive function on the IFN-γ production of CD4+ T cells in vivo. These findings indicating a mechanism by which BMP-4 may regulate activation and IFN-γ production in CD4+ T cells via metabolism moderation and suggests that BMP4 may be a potential therapeutic supplement in autoinflammatory diseases.

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3008 Role of Interferon-gamma in Natural Clearance of Chlamydia trachomatis Infection in Women

Journal of Clinical and Translational Science ◽

10.1017/cts.2019.260 ◽

2019 ◽

Vol 3 (s1) ◽

pp. 113-114

Author(s):

Stephen Jordan ◽

Lisa Coss ◽

Landon Wilson ◽

Stephen Barnes ◽

William Geisler ◽

...

Keyword(s):

T Cells ◽

Chlamydia Trachomatis ◽

Interferon Gamma ◽

Metabolic Pathways ◽

Cd4 T Cells ◽

Vaccine Development ◽

Intracellular Cytokine Staining ◽

Tryptophan Depletion ◽

Ifn Γ

OBJECTIVES/SPECIFIC AIMS: Chlamydia trachomatis (CT) infection can lead to reproductive morbidity in women. Animal models suggest that protection against CT is mediated through the cytokine interferon-gamma (IFN-γ), produced by CD4+ T-cells, which clears CT through intracellular tryptophan depletion. In humans, correlates of protection remain to be elucidated, which hinders chlamydia vaccine development. Natural clearance of CT infection (e.g., clearance before antibiotics) may be an immunological correlate of protection, evidenced by (1) CT clearance without antibiotics; and (2) a 4-fold reduced risk of CT reinfection within 6 months. We have identified women with and without natural clearance of CT infection. By comparing these two groups of women, the role of IFN-γ-mediated natural clearance of CT infection will be investigated. METHODS/STUDY POPULATION: Through collaboration with a cohort study of CT-infected women, we have access to stored specimens from women who naturally cleared CT or had persisting CT infection. Using peripheral blood mononuclear cell (PBMC), we will assess whether natural clearance of CT infection is associated with IFN-γ-producing CD4+ T-cells by stimulating PBMC ex vivo with CT antigens using intracellular cytokine staining. We will also use cervicovaginal lavage (CVL) and untargeted High-Performance Liquid Chromatography-Mass Spectrometry to assess for tryptophan-dependent and -independent metabolic pathways associated with natural clearance of CT infection. RESULTS/ANTICIPATED RESULTS:: To date, IFN-γ has been measured in 10 women who did not clear CT infection, demonstrating that <20% of these women produced significant levels of IFN-γ. Women who naturally cleared CT have yet to be studied. Untargeted HPLC-MS has been performed on 6 women (3 who cleared matched to 3 with persisting CT infection). To date, 11 pathways that are significantly associated with natural clearance have been identified. DISCUSSION/SIGNIFICANCE OF IMPACT: The outcome of natural clearance of CT infection is distinct from women with persisting chlamydia. These studies may inform whether IFN-γ, produced by CD4+ T-cells, or tryptophan-dependent or -independent metabolic pathways are associated with natural clearance, which may advance chlamydia vaccine development.

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Faculty Opinions recommendation of The contribution of transcription factor IRF1 to the interferon-gamma-interleukin 12 signaling axis and TH1 versus TH-17 differentiation of CD4+ T cells.

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

10.3410/f.1099170.555385 ◽

2008 ◽

Author(s):

Rachel R Caspi

Keyword(s):

T Cells ◽

Transcription Factor ◽

Interferon Gamma ◽

Cd4 T Cells ◽

Interleukin 12 ◽

Th 17 ◽

Signaling Axis

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HCA587 protein vaccine induces specific antitumor immunity mediated by CD4+ T-cells expressing granzyme B in a mouse model of melanoma

Anti-Cancer Agents in Medicinal Chemistry ◽

10.2174/1871520620666200728131951 ◽

2020 ◽

Vol 20 ◽

Author(s):

Weiming Yang ◽

Weiheng Zhang ◽

Xiaozhong Wang ◽

Liming Tan ◽

Hua Li ◽

...

Keyword(s):

T Cells ◽

Cd4 T Cells ◽

Antitumor Effect ◽

Granzyme B ◽

Cell Subset ◽

Cell Mediated Immunity ◽

Protein Vaccine ◽

Tumor Tissues ◽

Wide Range ◽

Ifn Γ

Background: The antigen HCA587 (also known as MAGE-C2), which is considered a cancer-testis antigen, exhibits upregulated expression in a wide range of malignant tumors with unique immunological properties, and may thus serve as a promising target for tumor immunotherapy. Objective: To explore the antitumor effect of the HCA587 protein vaccine and the response of humoral and cell-mediated immunity. Methods: The HCA587 protein vaccine was formulated with adjuvants CpG and and ISCOM. B16 melanoma cells were subcutaneously inoculated to C57BL/6 mice, followed by treatment with HCA587 protein vaccine subcutaneously. Mouse survival was monitored daily, and tumor volume was measured every 2 to 3 days. The tumor sizes, survival time and immune cells in tumor tissues were detected. And the vital immune cell subset and effector molecules were explored. Results: After treatment with HCA587 protein vaccine, the vaccination generated elicited significant immune responses, which delayed tumor growth and improved animal survival. The vaccination increased the proportion of CD4+ T cells expressing IFN-γ and granzyme B in tumor tissues. Depletion of CD4+T cells resulted in an almost complete abrogation of the antitumor effect of the vaccination, suggesting that the antitumor efficacy was mediated by CD4+ T cells. In addition, knockout of IFN-γ resulted in a decrease in granzyme B levels which were secreted by CD4+ T cells, and the antitumor effect was also significantly attenuated. Conclusion: The HCA587 protein vaccine may increase the levels of granzyme B expressed by CD4+ T cells, and this increase is dependent on IFN-γ, and the vaccine resulted in a specific tumor immune response and subsequent eradication of the tumor.

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Circulating CD4 T cells elicited by endemic coronaviruses display vast disparities in abundance and functional potential linked to both antigen specificity and age

The Journal of Infectious Diseases ◽

10.1093/infdis/jiab076 ◽

2021 ◽

Author(s):

Katherine A Richards ◽

Maryah Glover ◽

Jeremy C Crawford ◽

Paul Thomas ◽

Chantelle White ◽

...

Keyword(s):

T Cells ◽

Cd4 T Cells ◽

Protective Immunity ◽

Granzyme B ◽

Antigen Specificity ◽

Functional Potential ◽

Membrane Envelope ◽

Ifn Γ ◽

Human Coronaviruses ◽

Repeated Infections

Abstract Repeated infections with endemic human coronaviruses are thought to reflect lack of long-lasting protective immunity. Here, we evaluate circulating human CD4 T cells collected prior to 2020 for reactivity towards hCoV spike proteins, probing for the ability to produce IFN-γ, IL-2 or granzyme B. We find robust reactivity to spike-derived epitopes, comparable to influenza, but highly variable abundance and functional potential across subjects, depending on age and viral antigen specificity. To explore the potential of these memory cells to be recruited in SARS-CoV-2 infection, we examined the same subjects for cross-reactive recognition of epitopes from SARS-CoV-2 nucleocapsid, membrane/envelope, and spike. The functional potential of these cross-reactive CD4 T cells was highly variable, with nucleocapsid-specific CD4 T cells, but not spike-reactive cells showing exceptionally high levels of granzyme production upon stimulation. These results are considered in light of recruitment of hCoV-reactive cells into responses of humans to SARS-CoV infections or vaccinations.

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