Clonal expansion of T lymphocytes causes arthritis and mortality in mice infected with toxic shock syndrome toxin‐1‐producing staphylococci

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Abstract
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 Vβ elements. This finding provides a potential connection between staphylococcal exoproteins and endogenous immune mechanisms participating in the infectious process. We have recently described successful induction of infectious 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 Vβ11+ 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 Vβ11+ T cells proved to be of arthritogenic significance since mice genomically deleted of the Vβ11+ T cells did not develop arthritis and since pretreatment of healthy mice with anti-CD4 or anti-Vβ11 monoclonal antibodies inhibited arthritis. In addition, CD4+ and Vβ11+ 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+ Vβ11+ T cells is a driving pathogenic force.