Reduced Expression of TCR Zeta Is Involved in the Abnormal Production of Cytokines by Peripheral T Cells of Patients with Systemic Lupus Erythematosus

Abstract

Accumulating evidence suggests that dysfunction of T cells underlies the pathogenesis of systemic lupus erythematosus (SLE). We revealed that SLE T cells produced an abnormally excessive amount of IFN-γin vitro upon stimulation through TCR, and the expression level of TCR zeta was significantly reduced. The production of IFN-γ by SLE T cells was negatively correlated with the expression level of TCR zeta. This correlation was abolished when the cells were stimulated with TPA and ionomycin, which bypass TCR and introduce signals directly into the cells, but the production of IFN-γ by SLE T cells remained abnormally elevated. Taken together, these data suggest that regulatory mechanisms not only for the expression of TCR zeta but also for the production of IFN-γ were impaired in SLE T cells. These impairments may be responsible for the aberrant responses of SLE T cells and partly involved in the development of SLE.

T Lymphocytes from Chagasic Patients Are Activated but Lack Proliferative Capacity and Down-Regulate CD28 and CD3ζ

“…Down-regulation of CD3ζ has also been described in inflammatory or immune mediated diseases including rheumatoid arthritis [48], systemic lupus erythematosus [49] and leprous [50]. Interestingly, in these diseases the down-regulation CD3ζ-chain was associated with reduced IL-2 and IL-2R expression [26], [51], decreased proliferative capacity [52] and high IL-10 secretion [25], [53] on T cells.…”

Hematological Malignancy-Derived Small Extracellular Vesicles and Tumor Microenvironment: The Art of Turning Foes into Friends

“…Whiteside et al reported that TEVs mediate the inhibition of CD3ζ chain expression and drastically reduce its mRNA levels [106]. Decreased expression of the T-cell receptor (TCR) ζ-chain has been reported in several autoimmune, inflammatory and malignant diseases (e.g., lymphoma), and it is commonly associated with suppression of T cell proliferation and altered cytokine production [107,108,109,110]. During cancer progression, T cells are found in close contact with tumor cells and represent an essential component of the TME.…”

SLE-Associated Defects Promote Altered T Cell Function

“…This relationship between CD3ζ levels and cytokine polarization has also been observed in T cells from SLE patients where a negative correlation has been described between CD3ζ levels and IFN-γ production. 23…”