Up-regulated expression of Fas antigen (CD95) by peripheral naive and memory T cell subsets in patients with systemic lupus erythematosus (SLE): a possible mechanism for lymphopenia

Abstract

SUMMARY Fas antigen (CD95) is a membrane‐associated molecule that mediates apoptotic cell death and may play a role in the induction and maintenance of T cell tolerance. To elucidate the involvement of Fas antigen in human autoimmune diseases, we analysed Fas antigen expression by peripheral T cells from patients with SLE and rheumatoid arthritis (RA), using three‐colour flow cytometry. Both CD4+ and CD8+ T cell from SLE patients expressed Fas antigen in a higher density than did these cell from healthy donors and from RA patients. Enhancement of Fas antigen density was noted in Fas+CD45RO+ memory T cell from SLE patients. More remarkably, a significant expression of Fas antigen was observed in CD45RO− naive T cells from SLE patients CD4+CD45RO− T cells from SLE patients co‐expressed Fas antigen and early to intermediate activation antigens such as CD25 and CD71, and late activation antigen HLA‐DR in only FashiCD4+ naive T tells. Such up‐regulation of Fas antigen expression in SLE patients seems to be clinically meaningful, because mean fluorescence intensity (MFI) of Fas antigen on CD4+ T cell subsets inversely correlates with the absolute size of CD4+ T tell subsets in peripheral blood of SLE patients. These results suggest that T cells with increased Fas antigen expression may be highly susceptible to apoptotic cell death, in vivo. A putative mechanism for lymphopenia in SLE patients is discussed.

Increased Fas and Bcl‐2 Expression on Peripheral Blood T and B Lymphocytes from Juvenile‐Onset Systemic Lupus Erythematosus, but not from Juvenile Rheumatoid Arthritis and Juvenile Dermatomyositis

“…Increased expression of Fas antigen on CD3 þ T lymphocytes was also showed by Courtney et al (1999). Unlike the present results, Amasaki et al (1995) observed increased expression of Fas antigen on CD4 þ and CD8 þ T cells from lupus patients compared to healthy controls. Bijl et al (2001) also showed a higher expression of Fas protein on B lymphocytes from patients with lupus.…”

“…Mutations of Fas gene in MRL/Ipr mice lead to the development of a lymphoproliferative syndrome including features resembling lupus (RieaxLaucat et al 1995;Drappa et al 1996). Increased Fas expression has been reported on peripheral T and B cells from patients with lupus, on synovial fluid cells from patients with rheumatoid arthritis and on muscle fibres from patients with dermatomyositis (Ohsako et al 1994;Amasaki et al 1995;Behrens et al 1997;Sioud et al 1998;Sugiura et al 1999;Bijl et al 2001). Bcl-2 protein inhibits apoptosis (Ivanovska et al 2004).…”

Changes of memory B- and T-cell subsets in lupus nephritis patients

“…The reasons for decreased CD4+ lymphocyte count in SLE are, however, poorly understood. It may result from higher susceptibility of T-cells to apoptosis due to diminished expression of complement regulatory proteins or defective Fas/Fas-ligand system [39]. The depletion of lymphocytes may also be linked with anti-lymphocyte antibodies, which are detected in ~50% of SLE patients presenting with lymphopenia [40].…”

Heat shock protein 27 and its regulatory molecules express differentially in SLE patients with distinct autoantibody profiles

“…Increased rate of apoptosis of lymphocyte, macrophages, and monocytes are well documented in SLE [6][7][8]28]. Various extrinsic factors like Fas ligand [29], TNF related apoptosis inducing ligand (TRAIL) [30] and TNF related weak inducer of apoptosis (TWEAK) [31] also contribute to apoptosis in SLE. HSP27 is an important factor, which regulates both the intrinsic/extrinsic pathways of apoptosis [11,32].…”