Evidence for the Effects of a Superantigen in Rheumatoid Arthritis

Abstract

While studying the alpha beta T cell receptor repertoire in rheumatoid arthritis (RA) patients, we found that the frequency of V beta 14+ T cells was significantly higher in the synovial fluid of affected joints than in the peripheral blood. In fact, V beta 14+ T cells were virtually undetectable in the peripheral blood of a majority of these RA patients. beta-chain sequences indicated that one or a few clones dominated the V beta 14+ population in the synovial fluid of individual RA patients, whereas oligoclonality was less marked for other V beta's and for V beta 14 in other types of inflammatory arthritis. These results implicate V beta 14-bearing T cells in the pathology of RA. They also suggest that the etiology of RA may involve initial activation of V beta 14+ T cells by a V beta 14-specific superantigen with subsequent recruitment of a few activated autoreactive v beta 14+ T cell clones to the joints while the majority of other V beta 14+ T cells disappear.

Analysis of T cell receptor Vα and Vβ gene usage in synovia of patients with rheumatoid arthritis

“…In the earlier studies based on detection of Tcr-p chain gene rearrangements by Southern blotting, specific V genes could not be identified. A recent report of Vp use in peripheral blood and synovial fluid of RA patients found that Vpl 4 transcripts were barely detectable in PBMC of four of seven RA patients, but were significantly elevated in synovial fluid (26). However, in the present study Vpl4 transcripts were readily detected in both PBMC and SMC of all patients tested.…”

T Cell Influence on Superantigen‐Induced Arthritis in MRL‐lpr/lpr Mice

“…This model is consistent with a previous model of superantigen-induced RA in humans (14). In that model, the authors proposed that when the V,14-reactive superantigen is introduced into the systemic circulation, clonal deletion of self-reactive V, regions occurs.…”

“…Furthermore, it has been reported that some rheumatoid arthritis (RA) patients exhibit a clonal expansion of T cells in the synovial fluid. These T cells express T cell receptor (TCR) Vp14 (14) and other TCR specificities (14)(15)(16)(17)(18)(19)(20)(21)(22), which suggests that a superantigen(s) might be involved in the development of chronic arthritis. Not all RA patients exhibit a clonal expansion and activation of T cells, however (23,24).…”

“…Indeed, a large variety of V, or VDJ families have been reported to be overrepresented in the synovium of RA patients (14)(15)(16)(17)(18), and therefore a number of superantigens or nominal antigens may be involved in the initiation and perpetuation of RA. The results of the studies presented here suggest that the development of arthritis is facilitated by the presence of a large population of antigen-reactive T cells, as would be found for superantigens.…”

Skewed T-cell receptor BV14 and BV16 expression and shared CDR3 sequence and common sequence motifs in synovial T cells of rheumatoid arthritis

“…[13][14][15][16] Microbial antigens, such as mycobacterial antigens and staphylococcal superantigens, may also contribute to T-cell activation in RA. 17,18 However, it is unclear whether T-cell responses to any of these antigens are clinically relevant to RA.…”