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

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 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.

Major Histocompatibility Complex Class II Region Confers Susceptibility to Staphylococcus aureus Arthritis

“…MHC class II molecules could influence immune responses to staphylococci through their role in shaping the repertoire of mature T cells during T cell development [1], thus favouring the existence of pathogenic T cells. We have previously demonstrated that CD4 þ Vb11 þ TCR-expressing lymphocytes are of pathogenic significance in S. aureus-induced arthritis, since mice depleted of these cells displayed a lower frequency of disease [5]. In this respect, it is difficult to explain the differences between the groups of mice used in the present experiments through this mechanism, since there was no difference in the number of Vb11 þ cells in the inflamed joints between the groups.…”

Protective role of NK1.1+ cells in experimentalStaphylococcus aureusarthritis

“…Earlier studies have demonstrated the pivotal role of CD4 þ T cells in the progression of septic arthritis [8,9]. In the light of a recent report demonstrating that NK cells can play an important role in down-regulating Th1-mediated experimental colitis by controlling the responses of effector T cells to gut bacteria [28], we analysed the effect of in vivo NK cell depletion on T celldependent inflammation.…”

“…The role of lymphocytes in disease development has been extensively studied. Abdelnour et al have shown that T lymphocytes play a major pathogenic role in the disease [8,9]. Also, B lymphocytes contribute to arthritis, as shown in studies demonstrating that B cell-deficient Xid mice display a less severe arthritis [10].…”

Septic arthritis in Western and sub-Saharan African children - a review

“…Laboratory work with mice shows that strains of Staphylococcus that produce exoproteins (i.e., enterotoxin) cause more severe arthritis in infected joints than do strains that do not produce exoproteins [3]. Following on from this, it was discovered that specific inhibition of T-lymphocyte proliferation decreases the severity of arthritis, while generalised inhibition of the immune system increases the severity of arthritis [1,2]. This leads to the possibility that bacterial antigens and bacterial exotoxins stimulate Tlymphocyte proliferation and that this can occur even though the bacteria have been killed.…”