Ubiquitination system defects and abnormal tolerance in CD4+ T cells from systemic lupus erythematosus patients. (135.16)

Abstract

Abstract Ubiquitin ligases, such as Cbl-b, GRAIL and Itch are included in the anergy genetic program, and their deficiency in murine models has been related to a resistant to anergy phenotype in T cells and lupus like disease. The aim was to analyze Cbl-b, GRAIL and Itch expression in T cells from SLE patients upon anergy induction. We included 14 SLE patients in clinical remission and 5 active untreated SLE patients. Cbl-b RNA expression was measured by RT-PCR in peripheral CD4+ T cells from SLE patients and controls upon anergy induction (ionomycin). Cell proliferation was measured by CFSE. Cytokine production was analyzed by luminometry and activation markers surface expression by flow cytometry We show that CD4+ T cells from SLE patients display decreased expression of Cbl-b RNA upon anergy induction vs resting (p=0.020) and ex vivo (p=0.030) conditions. Also, a resistant to anergy phenotype (increased proliferation and IL-2 production upon ionomycin) was evidenced. Decreased IL-17 and IFN-γ production as well as increased CD69 expression were found in CD4+ T cells from SLE patients after anergy induction. The expression of GRAIL and Itch was not significantly altered. Our data suggest that CD4+ T cells from SLE patients in clinical remission display abnormalities in the ubiquitination system, specifically, deficient Cbl-b expression which is related to the resistant to anergy phenotype, and should be considered as part of the intrinsic T cell defects in SLE.