Enhanced susceptibility to superantigen-associated streptococcal sepsis inhuman leukocyte antigen-DQ transgenic mice

Bacterial superantigens are believed to cause septic shock, although, becau se of the lack of superantigen-sensitive infection models, proof that super antigenicity underlies shock pathogenesis is lacking. This work demonstrate s a clear superantigen effect in septic shock resulting from bacterial infe ction. Transgenic expression of human leukocyte antigen (HLA)-DQ, but not H LA-DR, specifically augments lymphocyte responses to streptococcal pyrogeni c exotoxin A (SPEA). HLA-DQ transgenic mice had increased mortality after a dministration of SPEA or infection with Streptococcus pyogenes. Immune acti vation during infection was HLA-DQ transgene-dependent and was manifested b y V beta -specific T cell repertoire changes and widespread lymphoblastic t issue infiltration. Unlike earlier models, which used toxin-induced shock, these T cell superantigen responses and lymphoblastoid changes were observe d during invasive streptococcal sepsis. Lymphoid activation was undetectabl e in HLA- DQ mice infected with an isogenic SPEA(-) strain, which proves th at a single superantigen can play a role in sepsis pathogenesis.