Increased expression and release of functional tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) by T cells from lupus patients with active disease

T Cell TRAIL Promotes Murine Lupus by Sustaining Effector CD4 Th Cell Numbers and by Inhibiting CD8 CTL Activity

“…Not only may TRAIL directly contribute to severity of lupus by promoting sustained CD4 ϩ T cell help for B cells, but it may also exacerbate disease by down-regulating perforin-mediated CTL activity, which in turn allows activated autoreactive B cells to escape deletion. The impaired elimination of autoantibody-producing host B cells in TRAIL-intact (WT3 F 1 ) compared with KO3 F 1 acute GVHD mice is consistent with reports in human lupus of increased membrane TRAIL on CD8 ϩ T cells (29,30) and defective in vitro CTL activity of CD8 ϩ T cells (62,63). Our results in chronic GVHD mice indicate that although a functional TRAIL molecule is required on CD4 ϩ T cells for sustaining lupus pathogenesis, it need not exhibit significant upregulation for lupus-like renal disease to develop.…”

“…In humans, we and others have previously identified TRAIL as part of the up-regulated genes belonging to the IFN-␣ signature in PBMC from SLE patients (27,28). Additionally, we have observed increased membrane-associated TRAIL on CD4 ϩ and CD8 ϩ T cells from lupus patients, which correlated with disease activity (30). Interestingly, in the present study, we observed that the induction of lupus-like disease in chronic GVHD mice was associated with low-level membrane TRAIL up-regulation on CD4 ϩ T cells and low-level elevations of IFN-␣ genes compared with values in acute GVHD mice.…”

“…Our group and others have demonstrated previously that SLE patients exhibit striking elevations in TRAIL gene expression (27,28). Moreover, both T cell-associated membrane TRAIL and release of soluble TRAIL are increased in SLE patients with active disease (7,29,30). These results strongly support a role for TRAIL in SLE pathogenesis; however, as with many of the immune abnormalities associated with lupus, it is not clear whether increased TRAIL expression reflects a compensatory mechanism aimed at limiting active disease or instead represents a mechanism central to disease exacerbation.…”

Increased expression of membrane TNF-α on activated peripheral CD8+ T cells in systemic lupus erythematosus

“…It is possible that membrane TNF-· is an effector molecule in addition to perforin and granzyme B in CD8+ T cells. Increased soluble and T cell-associated TNFrelated apoptosis-inducing ligand (TRAIL), a member of the TNF ligand family proteins like TNF-·, have been reported in active SLE patients (22). Considering its pro-apoptotic activity, TRAIL may amplify the abnormal apoptotic process in SLE.…”

The Relationship between Plasma sTRAIL Level and Disease Activity in Rheumatoid Arthritis

“…It is well known that TRAIL expression is enhanced in T cells and, as a result, monocyte apoptosis is increased in patients with SLE (7), whereas TRAIL-R1 is increased in ductal cells by IFN-g stimulation and these cells become susceptible to apoptosis in Sjogren's syndrome (8). It has been observed that the soluble TRAIL level is significantly higher in some neoplastic (9), infectious (10), and autoimmune diseases such as SLE (11)(12)(13) and ankylosing spondylitis (14,15).…”