T cell influence on superantigen-induced arthritis in MRL-lpr/lpr mice.
OBJECTIVE
To define the influence of the T cell receptor (TCR) and the lpr autoimmune gene on the induction and progression of superantigen-induced arthritis in V beta 8 transgenic MRL-lpr/lpr mice.


METHODS
The time to onset and the extent of synovial hyperplasia after the induction of arthritis by intraarticular injection of staphylococcal enterotoxin B (SEB) were compared in mice having T cells that bear the V beta 8 transgene alone (V beta 8 TCR transgenic MRL-+/+), the lpr gene without the V beta 8 gene (nontransgenic MRL-lpr/lpr), both the V beta 8 gene and the lpr gene (V beta 8 transgenic MRL-lpr/lpr), or neither gene (nontransgenic MRL-+/+). Synovial hyperplasia was compared in SEB-injected V beta 8 transgenic MRL-lpr/lpr mice after treatment with cyclosporin A (CSA), anti-V beta 8 and anti-CD4 monoclonal antibodies, and in V beta 8 transgenic MRL-lpr/lpr mice after injection of a non-V beta 8-reactive superantigen, staphylococcal enterotoxin A (SEA).


RESULTS
At day 30, increased synovial cells were observed in all SEB-treated mice, but the increase was greatest in the V beta 8 transgenic MRL-lpr/lpr mice. T cell involvement was indicated by the inability of either heat-denatured SEB or SEA to induce severe arthritis, the reduction in the severity of the arthritis on systemic treatment with CSA or anti-V beta 8, and the correlation of synovial hyperplasia with in vitro SEB reactivity of T cells.


CONCLUSIONS
These observations suggest that superantigens can induce chronic arthritis and that the induction and progression of the arthritis requires an underlying T cell defect in anergy induction in addition to exposure to the superantigen.
Mountz
J D
JD
Department of Medicine, University of Alabama at Birmingham 35294.
Zhou
T
T
Long
R E
RE
Bluethmann
H
H
Koopman
W J
WJ
Edwards
C K
CK
D000818:Animals; D001172:Arthritis, Rheumatoid / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology; D004195:Disease Models, Animal; D004768:Enterotoxins / Q000008:administration & dosage; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood; D007136:Immunoglobulins / Q000378:metabolism; D007270:Injections, Intra-Articular; D007719:Knee Joint; D051379:Mice; D008822:Mice, Transgenic / Q000276:immunology*; D010641:Phenotype; D011948:Receptors, Antigen, T-Cell; D018089:Superantigens / Q000009:adverse effects / Q000276:immunology; D013582:Synovial Fluid / Q000166:cytology; D013601:T-Lymphocytes / Q000502:physiology*; D015431:Weight Loss
D004768:Enterotoxins; D007074:Immunoglobulin G; D007136:Immunoglobulins; D011948:Receptors, Antigen, T-Cell; D018089:Superantigens; C031818:enterotoxin B, staphylococcal