CD49d marks Th1 and Tfh-like antigen-specific CD4 + T cells during Plasmodium chabaudi infection

2021 ◽  
Author(s):  
Jiun-Yu Jian ◽  
Shin-Ichi Inoue ◽  
Ganchimeg Bayarsaikhan ◽  
Mana Miyakoda ◽  
Daisuke Kimura ◽  
...  
Keyword(s):  
T Cells ◽  
Cd4 T Cells ◽  
White Pulp ◽  
Surrogate Markers ◽  
Plasmodium Infection ◽  
Plasmodium Chabaudi ◽  
Tfh Cells ◽  
Ifn Γ ◽  
Marginal Zones ◽  
Red Pulp

Abstract Upon activation, specific CD4 + T cells upregulate the expression of CD11a and CD49d, surrogate markers of pathogen-specific CD4 + T cells. However, using TCR transgenic mice specific for a Plasmodium antigen, termed PbT-II, we found that activated CD4 + T cells develop not only to CD11a hiCD49d hi cells, but also to CD11a hiCD49d lo cells during acute Plasmodium infection. CD49d hi PbT-II cells, localized in the red pulp of spleens, expressed transcription factor T-bet, and produced IFN-γ, indicating that they were Th1-type cells. In contrast, CD49d lo PbT-II cells resided in the white pulp/marginal zones and were a heterogeneous population, with approximately half of them expressing CXCR5 and a third expressing Bcl-6, a master regulator of Tfh cells. In adoptive transfer experiments, both CD49d hi and CD49d lo PbT-II cells differentiated into CD49d hi Th1-type cells after stimulation with antigen-pulsed dendritic cells, while CD49d hi and CD49d lo phenotypes were generally maintained in mice infected with P. chabaudi. These results suggest that CD49d is expressed on Th1-type Plasmodium-specific CD4 + T cells, which are localized in red pulp of the spleen, and can be used as a marker of antigen-specific Th1 CD4 + T cells, rather than that of all pathogen-specific CD4 + T cells.

scholarly journals Increased Th1 bias in memory T cells corresponds with protection from reinfection in Plasmodium infection, and is regulated by T cell-intrinsic STAT3

2019 ◽  
Author(s):  
Victor H. Carpio ◽  
Florentin Aussenac ◽  
Kyle D. Wilson ◽  
Alejandro V. Villarino ◽  
Alexander L. Dent ◽  
...  
Keyword(s):  
T Cells ◽  
Memory T Cells ◽  
Molecular Regulation ◽  
Plasmodium Infection ◽  
T Helper ◽  
T Helper 1 ◽  
Persistent Infections ◽  
Tfh Cells ◽  
Follicular Helper ◽  
Ifn Γ

SummaryHybrid Th1/Tfh cells (IFN-γ+IL-21+CXCR5+) predominate in response to persistent infections; however, molecular regulation of their function is poorly defined. In infection with Plasmodium spp, an IFN-γ+ T helper-1 (Th1) response controls initial parasitemia, while antibody and IL-21+CXCR5+ T follicular helper (Tfh) function effect final clearance. Here, we found that CD4-intrinsic Bcl6, Blimp-1 and STAT3 all regulate T-bet expression, which controls IFN-γ expression. While Bcl6 and Blimp-1 regulate the level of CXCR5, only T-bet and STAT3 affected the functional bias of the Th1/Tfh phenotype. Infected mice with STAT3-deficient T cells produced less antibody, and more IFN-γ+IL-21−CXCR5lo T cells, significantly increasing protection from re-infection. Conversely, reduced Th1 bias in re-infected T-bet KO was reflected in prolonged secondary parasitemia. In summary, each feature of hybrid Th1/Tfh population in Plasmodium infection is uniquely regulated and the cytokine bias of memory T cells can be modified to enhance the effectiveness of the response.

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

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.

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

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.

scholarly journals Splenic Stroma-Educated Regulatory Dendritic Cells Induce Apoptosis of Activated CD4 T Cells via Fas Ligand-Enhanced IFN-γ and Nitric Oxide

2011 ◽  
Vol 188 (3) ◽  
pp. 1168-1177 ◽  
Author(s):  
Xiongfei Xu ◽  
Hai Yi ◽  
Zhenhong Guo ◽  
Cheng Qian ◽  
Sheng Xia ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
T Cells ◽  
Dendritic Cells ◽  
Cd4 T Cells ◽  
Fas Ligand ◽  
Ifn Γ ◽  
Regulatory Dendritic Cells

scholarly journals Human Dendritic Cells Stimulated via TLR7 and/or TLR8 Induce the Sequential Production of Il-10, IFN-γ, and IL-17A by Naive CD4+ T Cells

2009 ◽  
Vol 182 (6) ◽  
pp. 3372-3379 ◽  
Author(s):  
Vincent Lombardi ◽  
Laurence Van Overtvelt ◽  
Stéphane Horiot ◽  
Philippe Moingeon
Keyword(s):  
T Cells ◽  
Dendritic Cells ◽  
Cd4 T Cells ◽  
Ifn Γ ◽  
Human Dendritic Cells

scholarly journals Human Zika infection induces a reduction of IFN-γ producing CD4 T-cells and a parallel expansion of effector Vδ2 T-cells

2017 ◽  
Vol 7 (1) ◽  
Author(s):  
Eleonora Cimini ◽  
Concetta Castilletti ◽  
Alessandra Sacchi ◽  
Rita Casetti ◽  
Veronica Bordoni ◽  
...  
Keyword(s):  
T Cells ◽  
Cd4 T Cells ◽  
Ifn Γ

scholarly journals IL-12 induced the generation of IL-21- and IFN-γ-co-expressing poly-functional CD4+ T cells from human naive CD4+ T cells

Cell Cycle ◽  
2015 ◽  
Vol 14 (21) ◽  
pp. 3362-3372 ◽  
Author(s):  
Sifei Yu ◽  
Lei Jia ◽  
Yannan Zhang ◽  
Junmin Zhong ◽  
Binyan Yang ◽  
...  
Keyword(s):  
T Cells ◽  
Cd4 T Cells ◽  
Ifn Γ

scholarly journals CRTAM determines the CD4+ cytotoxic T lymphocyte lineage

2015 ◽  
Vol 213 (1) ◽  
pp. 123-138 ◽  
Author(s):  
Arata Takeuchi ◽  
Mohamed El Sherif Gadelhaq Badr ◽  
Kosuke Miyauchi ◽  
Chitose Ishihara ◽  
Reiko Onishi ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cytotoxic Activity ◽  
Cd4 T Cells ◽  
Intracellular Signaling ◽  
Ectopic Expression ◽  
T Cell Subsets ◽  
Naive T Cells ◽  
Naïve T Cells ◽  
Ifn Γ

Naive T cells differentiate into various effector T cells, including CD4+ helper T cell subsets and CD8+ cytotoxic T cells (CTL). Although cytotoxic CD4+ T cells (CD4+CTL) also develop from naive T cells, the mechanism of development is elusive. We found that a small fraction of CD4+ T cells that express class I–restricted T cell–associated molecule (CRTAM) upon activation possesses the characteristics of both CD4+ and CD8+ T cells. CRTAM+ CD4+ T cells secrete IFN-γ, express CTL-related genes, such as eomesodermin (Eomes), Granzyme B, and perforin, after cultivation, and exhibit cytotoxic function, suggesting that CRTAM+ T cells are the precursor of CD4+CTL. Indeed, ectopic expression of CRTAM in T cells induced the production of IFN-γ, expression of CTL-related genes, and cytotoxic activity. The induction of CD4+CTL and IFN-γ production requires CRTAM-mediated intracellular signaling. CRTAM+ T cells traffic to mucosal tissues and inflammatory sites and developed into CD4+CTL, which are involved in mediating protection against infection as well as inducing inflammatory response, depending on the circumstances, through IFN-γ secretion and cytotoxic activity. These results reveal that CRTAM is critical to instruct the differentiation of CD4+CTL through the induction of Eomes and CTL-related gene.

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