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 staphylococca l infection. The reason(s) for the progressive course of the arthritis is unknown. It has been recently established that enterotoxins produc ed by Staphylococcus aureus display superantigen properties leading to stimulation of T cells carrying distinct T cell receptor V beta eleme nts. This finding provides a potential connection between staphylococc al exoproteins and endogenous immune mechanisms participating in the i nfectious 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 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 fn vitro culture system. The expansion of V beta 1 1(+) T cells proved to be of arthritogenic significance since mice gen omically 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 1 1 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 popu lations showed increased survival. We propose that in hematogenously s pread S. aureus-induced arthritis the TSST-1-dependent clonal expansio n of CD4(+) V beta 11(+) T cells is a driving pathogenic force.