1. Double-Edged Sword: Interleukin-2 Promotes T Regulatory Cell Differentiation but Also Expands Interleukin-13- and Interferon-γ-Producing CD8 + T Cells via STAT6-GATA-3 Axis in Systemic Lupus Erythematosus.
- Author
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Kato H and Perl A
- Subjects
- Adult, CD8-Positive T-Lymphocytes immunology, CD8-Positive T-Lymphocytes metabolism, Case-Control Studies, Cells, Cultured, Female, Humans, Interleukin-2 toxicity, Lupus Erythematosus, Systemic diagnosis, Lupus Erythematosus, Systemic metabolism, Male, Middle Aged, Phenotype, Phosphorylation, Signal Transduction, T-Lymphocytes, Regulatory immunology, T-Lymphocytes, Regulatory metabolism, CD8-Positive T-Lymphocytes drug effects, Cell Differentiation drug effects, Cell Proliferation drug effects, GATA3 Transcription Factor metabolism, Interferon-gamma metabolism, Interleukin-13 metabolism, Interleukin-2 pharmacology, Lupus Erythematosus, Systemic immunology, Lymphocyte Activation drug effects, STAT6 Transcription Factor metabolism, T-Lymphocytes, Regulatory drug effects
- Abstract
Interleukin-2 (IL-2) expands the depleted T regulatory (Treg) cell population, and it has emerged as a potential therapy in systemic lupus erythematosus (SLE). However, IL-2 administration may involve the risk of expanding unwanted pro-inflammatory cells. We herein studied the effects of IL-2 on pro-inflammatory cytokine production by CD4
+ and CD8+ T cells in parallel with Treg development following CD3/CD28 co-stimulation. While Treg cells are depleted in SLE patients, their CD4+ T cells were poised to receive and activate IL-2 signaling as evidenced by upregulation of CD25 and enhanced IL-2-incued STAT5 phosphorylation during Treg differentiation. In patients with SLE, however, IL-2 also expanded CD8+ T cells capable of producing interleukin-5, interkeukin-13 (IL-13), and interferon-γ (IFN-γ) that occurred with enhanced expression of GATA-3 and phosphorylation of STAT6 but not STAT5. Our data pinpoint a safety signal for systemic administration of IL-2 and challenges a long-held conceptual platform of type 1 and 2 cytokine antagonism by newly documenting the IL-2-dependent development of IL-13 and IFN-γ double-positive (IL-13+ IFNγ+ ) CD8+ T cells in SLE., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Kato and Perl.)- Published
- 2021
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