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.
Highlights
Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by aberrant T- and Bcell activation culminating in a production of antinuclear antibodies [1]
To confirm the essentiality of IL-2 signaling in T regulatory (Treg) differentiation in SLE, naïve CD4+ T cells were cultured under Treg-polarizing conditions in the presence or absence of IL-2 or anti-IL-2
SLE CD4+ T cells are primed to receive and activate IL-2 signaling as evidenced by the upregulation of CD25 and increased IL-2-induced STAT5 phosphorylation under Treg-polarizing conditions, Treg cells are depleted in SLE patients (Figure 1C)
Summary
Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by aberrant T- and Bcell activation culminating in a production of antinuclear antibodies [1]. Among numerous immune dysregulation pathways implicated in the pathogenesis, the depletion of T regulatory (Treg) cells has emerged as an important mediator of the disease [2,3,4]. In this respect, interleukin (IL)-2 elicits T regulatory (Treg) cell differentiation in association with phosphorylation of STAT5 and its binding. IL-2 Induces IL-13+IFN-g+ CD8+ T Cells to the Foxp gene [5] These findings along with IL-2 deficiency in lupus patients [6] yielded the notion that supplementation of IL-2 could restore the immune tolerance by expanding the Treg cell population.
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
