Owing to their mode of action, superantigens have been identified as a possible candidate for one of the causative agents of autoimmune disease (2,61). Because autoreactive T and B cells can easily be isolated from the peripheral blood of healthy individuals (62,63), superantigens could stimulate auto-reactive T cells both locally and systemically, since they do not discriminate between autoimmune and normal lymphocytes (64). Thus the delicate balance of tolerance could be broken. Although superantigens are yet to be directly implicated in human autoimmune disease, there is growing evidence to suggest their involvement. For example, SED and SED-reactive T cell lines have been shown to stimulate auto-antibody production by B cells in vitro (65). It has been shown that Staphylococcus aureus strain AB-1 is responsible for the spontaneous outbreak of staphylococcal arthritis in a colony of rats (66). When this strain was isolated from a swollen joint and injected intravenously into healthy rats, erosive, persistent arthritis developed in a majority of the rats. The arthritic lesions were characterized by the infiltration of T cells into the synovium. These T cells were later shown to be activated by a superantigen present in the infectious pathogen (67).
In the absence of infection, injection of low doses of SEA or SEB induces relapsing paralysis in Experimental Autoimmune Encephalomyelitis (EAE), the animal model of multiple sclerosis (68). Further studies have shown that SEB can induce MBP-specific T cells expressing different Vp to respond to myelin-antigens and mediate this relapsing paralysis (69). Autoimmune conditions such as arthritis, diabetes, and multiple sclerosis are characterized by heterogeneous T cell infiltrates during active bouts of the disease. This implies that a broad spectrum of superantigens could cause this exacerbation (70). Type I diabetes is associated with a retroviral superantigen, which is thought to activate and expand T cells carrying the TCR Vp7 element, which in turn has been implicated in the pathogenesis of insulin dependent diabetes mellitus (71).
Recently, the first case of type I diabetes associated with a bacterial superantigen-mediated disease was reported (72). However, it still remains unclear whether superantigens are the initial trigger of autoimmune disease; as environmental factors that can change a controllable illness into one that becomes relentless for susceptible individuals.
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