T cells as therapeutic targets in SLE.
T cells contribute to the initiation and perpetuation of autoimmunity in systemic lupus erythematosus (SLE), and seem to be directly involved in the development of related organ pathology. Defects associated with CD8(+) and T-regulatory (T(REG)) cell function manifest in parallel with the expanded CD3(+)CD4(-)CD8(-) T cell lineage. The cytokine expression pattern is uniquely characterized by decreased expression of interleukin (IL)-2 and increased production of IL-17 and related cytokines. Therapeutic approaches that limit the cognate interaction between T cells and B cells, prevent inappropriate tissue homing and restore T(REG) cell function and the normal cytokine milieu have been entertained. Biochemical characterization of SLE T cells has revealed distinct early and late signaling aberrations, and has enabled the identification of novel molecular targets that can be corrected with small molecules, and biomarkers that may foretell disease activity and predict organ damage.
Crispín
José C
JC
Division of Rheumatology, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, 330 Brookline Avenue, Boston, MA 02115, USA.
Kyttaris
Vasileios C
VC
Terhorst
Cox
C
Tsokos
George C
GC
D000818:Animals; D001691:Biological Therapy; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000188:drug therapy* / Q000276:immunology*; D015398:Signal Transduction / Q000187:drug effects / Q000276:immunology; D013601:T-Lymphocytes / Q000187:drug effects* / Q000276:immunology*
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