Cloning and characterization of a cDNA for a new mouse T cell growth factor (P40).

Snick, Jacques Van; Goethals, A.; Renauld, Jean‐Christophe; Roost, Emiel Van; Uyttenhove, Catherine; Rubira, Michael R.; Moritz, Robert L.; Simpson, Richard J.

doi:10.1084/jem.169.1.363

Cited by 161 publications

(64 citation statements)

References 17 publications

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“…Previous studies, largely involving mouse models, have suggested that the common denominator of IL-9 function is to promote the survival of different cell types, including T cells [44] Furthermore, our results indicate that IL-9 treatment maintains, rather than induces, DP T-cell proliferation. These data are in accordance with Houssiau's results [33] indicating that the human T-cell proliferative responses to IL-9 require previous activation.…”

Section: Discussionsupporting

confidence: 65%

“…Previous studies, largely involving mouse models, have suggested that the common denominator of IL-9 function is to promote the survival of different cell types, including T cells [44], mast cells [35], and eosinophils [45] as well as neurons [46], tumors [47], and epithelial cells [48]. Here, we clearly showed that IL-9 decreased the degree of apoptosis of human intra-tumor DP T cells following growth factor withdrawal.…”

Section: Discussionsupporting

confidence: 56%

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IL‐9 promotes the survival and function of human melanoma‐infiltrating CD4⁺CD8⁺ double‐positive T cells

et al. 2016

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We previously demonstrated an accumulation of tumor-reactive CD4 + CD8 + double positive (DP) T cells within melanoma-infiltrating lymphocytes, supporting their role in the regulation of anti-tumor immune responses. Similarly to their CD8 + counterparts, intratumor DP T cells are MHC class-I restricted but differed by a limited lytic activity against autologous melanoma cells. Based on these observations and to further characterize DP T cells, both populations were compared at the transcriptional level. Our results revealed the overexpression of the IL-9 receptor (IL-9R) by DP T cells and prompted us to investigate the impact of IL-9 on their biology. We show that IL-9 favors DP T-cell survival by protecting them from apoptosis and by promoting their proliferation. In addition, IL-9 enhances their ability to produce cytokines and increased their levels of granzyme B/perforin as well as degranulation capacity, leading to a strengthened cytotoxic activity against melanoma cells. Taken together, the IL-9R high DP T-cell population could be a new preferential target for IL-9, which could take part in their retention within the melanoma infiltrate while also favoring their anti-tumor activity. More generally, our results extend the pleiotropic effects of IL-9 to IL-9R-expressing intra-tumor T cells, which could further potentiate anti-tumor immune responses.Keywords: CD4 + CD8 + double-positive T lymphocyte r IL-9R r IL-9 r Melanoma r TIL Additional supporting information may be found in the online version of this article at the publisher's web-site Correspondence: Dr. Nadine Gervois e-mail: nadine.gervois@inserm.fr IntroductionPeripheral CD4 + CD8 + double-positive (DP) T cells were first identified 25 years ago as a mature T-cell subpopulation accounting for about 1-2% of total T cells within healthy donor PBMCs Eur. J. Immunol. 2016Immunol. . 46: 1770Immunol. -1782 Tumor immunology 1771 with age-dependent increase [2]. Since then, DP T cells have been described as a highly heterogeneous population with at least three subsets based on the expression levels of the CD4 and the CD8 coreceptors (CD4 high CD8 low , CD4 low CD8 high , CD4 high CD8 high ) and on the nature of the CD8 dimer (αα or αβ) [3]. Regarding DP T cells lineage origin, two main hypotheses are still in debate. Some studies argued they step from a premature release of DP T cells from the thymus into the periphery, where their maturation into functionally competent single-positive (SP) cells continues [4,5].Others studies hypothesized that they could derive from peripheral single positive T cells. As such, IL-4 represents an important mediator of CD8αα induction on human SP CD4 T cells [6]. On the other hand, when activated in vitro via TCR cross-linking, SP CD8αβ T cells may become capable of expressing low levels of CD4 [7,8].Of interest, numerous studies reported the presence of DP T cells with, in most cases, an increased frequency in the blood and/or in the target organ of several pathological conditions (for review see [9]), such as autoimmune ...

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Section: Discussionsupporting

confidence: 65%

“…Previous studies, largely involving mouse models, have suggested that the common denominator of IL-9 function is to promote the survival of different cell types, including T cells [44], mast cells [35], and eosinophils [45] as well as neurons [46], tumors [47], and epithelial cells [48]. Here, we clearly showed that IL-9 decreased the degree of apoptosis of human intra-tumor DP T cells following growth factor withdrawal.…”

Section: Discussionsupporting

confidence: 56%

IL‐9 promotes the survival and function of human melanoma‐infiltrating CD4⁺CD8⁺ double‐positive T cells

et al. 2016

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“…IL-9 was originally described as a murine T cell growth factor (21). Human and murine IL-9 are 126 amino acids long (21,22).…”

mentioning

confidence: 99%

“…Human and murine IL-9 are 126 amino acids long (21,22). IL-9 is produced by activated T cells and supports the growth of Th clones but not cytolytic clones (23,24).…”

mentioning

confidence: 99%

Signals from the IL-9 Receptor Are Critical for the Early Stages of Human Intrathymic T Cell Development

Smedt

Verhasselt

Kerre

et al. 2000

The Journal of Immunology

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Highly purified human CD34+ hemopoietic precursor cells differentiate into mature T cells when seeded in vitro in isolated fetal thymic lobes of SCID mice followed by fetal thymus organ culture (FTOC). Here, this chimeric human-mouse FTOC was used to address the role of IL-9 and of the α-chain of the IL-9 receptor (IL-9Rα) in early human T cell development. We report that addition of the mAb AH9R7, which recognizes and blocks selectively the human high affinity α-chain of the IL-9R, results in a profound reduction of the number of human thymocytes. Analysis of lymphoid subpopulations indicates that a highly reduced number of cells undergo maturation from CD34+ precursor cells toward CD4+CD3−CD8−CD1+ progenitor cells and subsequently toward CD4+CD8+ double positive (DP) thymocytes. Addition of IL-9 to the FTOC resulted in an increase in cell number, without disturbing the frequencies of the different subsets. These data suggest that IL-9Rα signaling is critical in early T lymphoid development.

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“…Th9 cells differentiate from naive Th cells in the presence of both TGF-b and IL-4, or from Th2 cells in the presence of TGF-b (6). IL-9 influences many cell types, including T cells, B cells, mast cells, eosinophils, lung epithelial cells, and hematopoietic progenitors (7)(8)(9)(10). The essential roles of IL-9 in the pathogenic progression of type I hypersensitivity have been demonstrated using IL-9-transgenic mice and IL-9-deficient mice.…”

mentioning

confidence: 99%

Calcitonin Gene-Related Peptide and Cyclic Adenosine 5′-Monophosphate/Protein Kinase A Pathway Promote IL-9 Production in Th9 Differentiation Process

Mikami

Miyagi

Sueda

et al. 2013

The Journal of Immunology

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Th9 cells are a novel Th cell subset that produces IL-9 and is involved in type I hypersensitivity such as airway inflammation. Although its critical roles in asthma have attracted interest, the physiological regulatory mechanisms of Th9 cell differentiation and function are largely unknown. Asthma is easily affected by psychological factors. Therefore, we investigated one of the physiological mediators derived from the nervous system, calcitonin gene-related peptide (CGRP), in asthma and Th9 cells because CGRP and activation of the cAMP/protein kinase A (PKA) pathway by CGRP are known to be important regulators in several immune responses and allergic diseases. In this study, we demonstrated that the CGRP/cAMP/PKA pathway promotes IL-9 production via NFATc2 activation by PKA-dependent glycogen synthase kinase-3β inactivation. Moreover, CGRP also induces the expression of PU.1, a critical transcriptional factor in Th9 cells, which depends on PKA, but not NFATc2. Additionally, we demonstrated the physiological importance of CGRP in IL-9 production and Th9 differentiation using an OVA-induced airway inflammation model and T cell–specific CGRP receptor-deficient mice. The present study revealed a novel regulatory mechanism comprising G protein–coupled receptor ligands and nervous system-derived substances in Th9 cell differentiation and type I hypersensitivity.

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Cloning and characterization of a cDNA for a new mouse T cell growth factor (P40).

Cited by 161 publications

References 17 publications

IL‐9 promotes the survival and function of human melanoma‐infiltrating CD4⁺CD8⁺ double‐positive T cells

IL‐9 promotes the survival and function of human melanoma‐infiltrating CD4⁺CD8⁺ double‐positive T cells

Signals from the IL-9 Receptor Are Critical for the Early Stages of Human Intrathymic T Cell Development

Calcitonin Gene-Related Peptide and Cyclic Adenosine 5′-Monophosphate/Protein Kinase A Pathway Promote IL-9 Production in Th9 Differentiation Process

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Cloning and characterization of a cDNA for a new mouse T cell growth factor (P40).

Cited by 161 publications

References 17 publications

IL‐9 promotes the survival and function of human melanoma‐infiltrating CD4+CD8+ double‐positive T cells

IL‐9 promotes the survival and function of human melanoma‐infiltrating CD4+CD8+ double‐positive T cells

Signals from the IL-9 Receptor Are Critical for the Early Stages of Human Intrathymic T Cell Development

Calcitonin Gene-Related Peptide and Cyclic Adenosine 5′-Monophosphate/Protein Kinase A Pathway Promote IL-9 Production in Th9 Differentiation Process

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IL‐9 promotes the survival and function of human melanoma‐infiltrating CD4⁺CD8⁺ double‐positive T cells

IL‐9 promotes the survival and function of human melanoma‐infiltrating CD4⁺CD8⁺ double‐positive T cells