Clonal expansion of T lymphocytes causes arthritis and mortality in mice infected with toxic shock syndrome toxin-1-producing staphylococci.
Erosive arthritis is a common and feared complication of staphylococcal infection. The reason(s) for the progressive course of the arthritis is unknown. It has been recently established that enterotoxins produced by Staphylococcus aureus display superantigen properties leading to stimulation of T cells carrying distinct T cell receptor V beta elements. This finding provides a potential connection between staphylococcal exoproteins and endogenous immune mechanisms participating in the infectious process. We have recently describe successful induction of infections arthritis in mice after intravenous inoculation of a toxic shock syndrome toxin-1 (TSST-1)-producing S. aureus LS-1 strain. Using this model we have now found a clonal expansion of T cells expressing V beta 11+ T cell receptor in the synovial tissue of arthritic mice. The role of TSST-1 as a superantigen inducing oligoclonal expansion was confirmed in an in vitro culture system. The expansion of V beta 11+ T cells proved to be of arthritogenic significance since mice genomically deleted of the V beta 11+ T cells did not develop arthritis and since pretreatment of healthy mice with anti-CD4 or anti-V beta 11 monoclonal antibodies inhibited arthritis. In addition, CD4+ and V beta 11+ T cells showed themselves to be of pathogenic significance in staphylococcal-induced mortality, since mice depleted of such populations showed increased survival. We propose that in hematogenously spread S. aureus-induced arthritis the TSST-1-dependent clonal expansion of CD4+ V beta 11+ T cells is a driving pathogenic force.
Abdelnour
A
A
Department of Clinical Immunology, University of Göteborg, Sweden.
Bremell
T
T
Holmdahl
R
R
Tarkowski
A
A
D000818:Animals; D001170:Arthritis, Infectious / Q000276:immunology*; D016470:Bacteremia / Q000276:immunology / Q000401:mortality; D001427:Bacterial Toxins; D002478:Cells, Cultured; D004768:Enterotoxins / Q000502:physiology*; D007124:Immunoenzyme Techniques; D008297:Male; D051379:Mice; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000502:physiology; D013154:Spleen / Q000166:cytology; D013203:Staphylococcal Infections / Q000276:immunology* / Q000401:mortality; D018089:Superantigens; D016176:T-Lymphocyte Subsets / Q000276:immunology*
D001427:Bacterial Toxins; D004768:Enterotoxins; D016693:Receptors, Antigen, T-Cell, alpha-beta; D018089:Superantigens; C030107:enterotoxin F, Staphylococcal