- Paper Report
- Open Access
SLE apoptosis and hyporesponsiveness to gammac-chain cytokines
- Sylvie Fournel1
© Biomed Central Ltd 2002
- Received: 31 May 2002
- Accepted: 5 July 2002
- Published: 11 July 2002
- gamma-c cytokines
A recent hypothesis suggests that dysregulation of apoptosis explains the development of autoimmune disease. Indeed, various authors have described an excess of apoptotic bodies in lupus patients after, for example, UV-irradiation. To explain this, two mechanisms have been proposed: (i) an increase in apoptosis, and (ii) a decrease of apoptotic-cell clearance. The dysregulation of apoptotic-cell clearance has been supported by various experiments. In contrast accelerated apoptosis of lymphocytes in vitro has been described but was not specific to systemic lupus erythematosus (SLE) patients. However, these experiments were performed with lymphocytes from "healthy" SLE patients, and lupus disease activity frequently increases during the course of an infection. To test the implications of infection on apoptosis dysregulation, these authors investigated apoptosis of activated lymphocytes of SLE patients suffering from an acute infection.
When cultured, an increased number of peripheral blood mononuclear cells (PBMC) from patients suffering from an infection were apoptotic, in comparison to PBMCs from healthy controls or from patients with other autoimmune diseases. Apoptosis levels returned to baseline at the end of infection. In comparison to activated lymphocytes from healthy controls, in vitro activated lymphocytes from SLE patients showed hyporesponsiveness to IL-2 and IL-7, but not to IL-4 and IL-15; however, this response is not specific for SLE patients. In contrast, apoptosis of resting lymphoblasts from SLE patients was not inhibited by addition of gammac-chain cytokines (IL-2, IL-4, IL-7 and IL-15), whereas all these cytokines inhibited apoptosis of healthy control lymphoblasts. IL-2 and IL-15 inhibited apoptosis of lymphoblasts from patients with other autoimmune diseases. This hyporesponsivness to gammac-chain cytokines is more important if cells are derived from patients during a phase of high serological activity, or from patients with Th1 dominant cytokine profiles in their serum (e.g., high IL-12, detectable IFN-gamma).
cell culture, measurement of apoptosis
- Lorenz HM, Grunke M, Hieronymus T, Winkler S, Blank N, Rascu A, Wendler J, Geiler T, Kalden JR: Hyporesponsiveness to gammac-chain cytokines in activated lymphocytes from patients with systemic lupus erythematosus leads to accelerated apoptosis. Eur J Immunol. 2002, 32: 1253-1263.PubMedView ArticleGoogle Scholar