CUTANEOUS EXPOSURE TO THE SUPERANTIGEN STAPHYLOCOCCAL-ENTEROTOXIN-B ELICITS A T-CELL-DEPENDENT INFLAMMATORY RESPONSE

We analyzed the impact of superantigens secreted by skin-colonizing St aphylococci on the skin and the associated lymphoid tissue following e picutaneous application and intracutaneous injection of small amounts of staphylococcal enterotoxin B (SEB). A single intracutaneous injecti on of 50 ng of SEB elicited a strong inflammatory response in the skin of BALB/c mice. Three to 6 h later, we observed Langerhans cell activ ation, mast cell degranulation, vasodilation, upregulation of ICAM-1, and induction of VCAM-1 on dermal blood vessels, with vascular adhesio n of granulocytes. By 12 to 24 h, cell infiltration of the dermis incr eased, reaching the epidermis. Among the infiltrating leukocytes, a su bstantial number of eosinophils was found. After 48 h, the infiltrate was dominated by mononuclear cells. The response to SEB was dose-depen dent, and signs of inflammation slowly disappeared over 5 to 7 days. A lthough the induction of VCAM-1 on dermal blood vessels suggested a ro le for interleukin-1/tumor necrosis factor-alpha in this reaction, the activation of monocytes/macrophages was not able to substitute for ly mphocytes, as severe combined immunodeficiency (SCID) mice (which are lymphocyte-deficient) did not mount an inflammatory skin response to i ntradermal injection of SEB. The fact that nude mice (T-cell-deficient ) also did not mount an inflammatory response to SEB indicated the T-c ell dependency of the response. The V beta specificity of the SEB effe ct was demonstrated by the fact that SJL/J mice, which lack V beta 8() T cells (the major SEB-reactive T cell population in mice), exhibite d much weaker responses. Deletion or tolerization of SEB-reactive V be ta T cells was not observed after a single intradermal injection of su ch minute amounts of SEB.