Immunomodulation of Experimental Autoimmune Encephalomyelitis by Staphylococcal Enterotoxin D
ABSTRACT Staphylococcal enterotoxins (SEs) can bind major histocompatibility antigens and stimulate T cells which bear particular types of T cell receptor. Therefore, it has been postulated that SEs may trigger or modulate the development of autoimmune diseases caused by T cells. In the present study, we examined the effects of SEs on rat encephalitogenic T cells and the clinical manifestation of experimental autoimmune encephalomyelitis (EAE). SED, but not other SEs, stimulated encephalitogenic T cells. Furthermore, culture of lymphoid cells from myelin basic protein (MBP)-immunized rats with SED augmented the clinical manifestation of passively transferred EAE, whereas SEA and SEB showed no significant EAE-transfer ability. Flow cytometric analysis demonstrated that in vitro SED stimulation of T cells from MBP-immunized rats, but not from normal rats, resulted in selective expansion of V beta 8.2+ T cells. Consistent with in vitro findings, in vivo administration of SED modulated EAE elicited by immunization with MBP. SED given after the immunization augmented clinical manifestation, especially at low doses. On the other hand, SED given 7 days before the immunization suppressed the development of EAE in a dose-dependent manner. Interestingly, the same toxin given at a dose of 20 micrograms to thymectomized rats induced enhanced EAE regardless of the timing of administration. It has already been established that SEs stimulate T cells bearing a particular type of TCR V beta chain and subsequently induce unresponsiveness of these T cells. The present results suggest that a similar mechanism may operate in rats after the toxin treatment and MBP immunization. However, in vitro assay showed that the proliferative responses of T cells from EAE-suppressed rats to MBP and SED were not eliminated, suggesting that SED-induced suppressor T cells may also play some roles in EAE suppression. The present study has shown that SED, one of the superantigens, modulates an autoimmune disease. More importantly, its effects are not uniform, but instead are closely related to the dose of the toxin, timing of toxin exposure, and the status of hosts.
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Article: In vivo effects of superantigens[Show abstract] [Hide abstract]
ABSTRACT: Superantigens are potent immunostimulatory molecules that activate both T cells and antigen presenting cells. The consequences of superantigen exposure range from induction of T cell proliferation, massive cytokine release and systemic shock to immunosuppression and tolerance. Superantigens have been directly implicated in a number of human conditions including food poisoning and toxic shock. In addition, there is evidence to suggest that superantigens are involved in the initiation of autoimmunity, and the immune dysfunction associated with HIV infection. Because of their possible role in human disease, and their potential use in immune therapy, it is important that we more completely understand the in vivo effects of superantigens.Life Sciences 02/1995; 57(19):1717-35. DOI:10.1016/0024-3205(95)02045-K · 2.30 Impact Factor
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