Immune cells and cytokines in systemic lupus erythematosus: an update.
OBJECTIVE
Systemic lupus erythematosus is characterized by overactive B cells that differentiate into autoantibody-forming cells, aberrant T cell function that provides help to B cells, and the production of pro-inflammatory cytokines. This article reviews recent studies unraveling the complex interplay between cytokines and lymphocytes in systemic lupus erythematosus.


RESULTS
In systemic lupus erythematosus, T cells are characterized by heightened calcium responses early after activation of their surface receptor. Alterations of the T cell receptor/CD3 complex, namely the substitution of the FcepsilsonRgamma for the T cell receptor zeta chain, and increased mitochondrial potentials can account for this 'overexcitable' phenotype. At the same time, this heightened calcium signal leads to a block of the transcription of the IL-2 gene, a pivotal cytokine for the immune response. The end result is increased spontaneous apoptosis and decreased activation-induced cell death of T cells in systemic lupus erythematosus that in turn leads to enhanced help to B cells and potentially decreased regulatory function. The B cells, on the other hand, are shown to be directly activated by immune complexes by way of Toll-like receptors independently of T cells. Finally, recent studies have tried to elucidate the role of cytokines such as interferon-alpha in systemic lupus erythematosus and, following the paradigm of rheumatoid arthritis, to establish targets for treatment.


CONCLUSIONS
The increased apoptosis and aberrant T cell activation coupled with nonspecific activation of B cells lead to the production of auto-antigen: auto-antibody complexes that are the hallmark of systemic lupus erythematosus. Future treatments aiming at correcting the intracellular and intercellular signaling abnormalities may prove effective in restoring immune tolerance in systemic lupus erythematosus.
Kyttaris
Vasileios C
VC
Department of Cellular Injury, Walter Reed Army Institute of Research, Silver Spring, Maryland, USA.
Juang
Yuang-Taung
YT
Tsokos
George C
GC
D001402:B-Lymphocytes / Q000276:immunology*; D016207:Cytokines / Q000276:immunology*; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*
D016207:Cytokines