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Review
. 2015 Apr;24(4-5):351-63.
doi: 10.1177/0961203314556139.

T cells as a therapeutic target in SLE

D Comte  1 , M P Karampetsou  2 , G C Tsokos  2
Affiliations
Review

T cells as a therapeutic target in SLE

D Comte et al. Lupus. 2015 Apr.

Abstract

Systemic lupus erythematosus (SLE) is a multisystem autoimmune disease characterized by a loss of tolerance to multiple endogenous antigens. SLE etiology remains largely unknown, despite recent insight into the immunopathogenesis of the disease. T cells are important in the development of the disease by amplifying the immune response and contributing to organ damage. Aberrant signaling, cytokine secretion, and tissue homing displayed by SLE T cells have been extensively studied and the underlying pathogenic molecular mechanisms are starting to be elucidated. T-cell-targeted treatments are being explored in SLE patients. This review is an update on the T-cell abnormalities and related therapeutic options in SLE.

Keywords: Systemic lupus erythematosus; T cells; epigenetics; interleukin-2 (IL-2); treatment.

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Figures

Figure 1
Figure 1. Aberrant signaling events in SLE T cells and potential therapeutic targets
The lupus T cell is characterized by the downregulation of CD3ζ chain and its substitution by the FcRγ common chain. Following stimulation, FcRγ associates with Syk kinase, instead of ZAP-70, leading to heightened calcium responses and aberrant activation of calcineurin and CaMKIV. The increased magnitude of the early signaling events leads to a misbalance of the transcriptional machinery and results in aberrant gene expression. The white arrows with the star indicate potential therapeutic targets that are currently being considered for the management of SLE.
Figure 2
Figure 2. T cells differentiation and cytokines aberration in SLE patients
The cytokines produced by macrophages, antigen-presenting cells (APC), B cells, neutrophils and activated T cells, along with the decreased IL-2, influence the development of naïve CD4+ T cells in SLE patients. These alterations favor the development of Th17, TCRab+CD4-CD8 double negative (DN) and T follicular helper (TFH) T cells, whilst inhibiting regulatory T cells (TREG) differentiation. Collectively, these abnormalities enhance B cell maturation and differentiation, antibody production and immune complex formation, and also promote organ damage. Arrows indicate increased/decreased cytokines or cell subset in SLE compared to control.
See this image and copyright information in PMC

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