Analysis of the in vivo dend ritic cell response to the bacterial superantigen staphylococcal enterotoxin B in the mouse spleen

Abstract

To inv esti ga te th e in vi vo effec ts of St<l ph ylococca l enterotoxin B (SEB) on dendritic ce lls (DCs) in the splee n, a single dose of SEB (50 pg/kg) was administered to BALB/c mice by intraperi to nea l injection. Aft erwa rds, the mice were sacrificed at 2, 6 and 24 hr, 2, 4, 7 and 15 days, and the splee ns were removed. The immunocytochemica l characterizati on of th e ce lls was ca rri ed out usin g va ri ous monocl onal anti bodi es in cryostat-cut sect ions. The distributi on patt erns of DCs and th eir ma jor costimulatory molecul es, CD80, CD86 and CD40 in the spleen were identified, and the ev idence fo r maturation of DCs ill vivo in response to SEB was obtained. It was found that systemic administration of SEB induced the migration of most of the immature, splenic DCs from the marginal zone to the periarterial lymphatic sheath wjthin 6 hr. This movement paralleled a maturation process, as assessed by upregul ati on of CD40, CD80 and CD86 ex pression in the interdigitating dendritic cells (IDCs). The upregul ation of costimul atory molecul e expression was co nspi c uous o nl y in DCs in co ntrast to oth e r antige n- prese nting ce lls (APCs) such as mac rophages and B ce lls w hi c h did no t s how a ny sig nifica nt altera tions in their costimulatory molecul e expression. We also demonstrated the temporal expression pattern of these costimulatory molecul es on the activated DCs. The upregul ation of costimulatory molecul es on DCs reached a peak leve l 6 hr aft er SEB injection, while the increase in number of T ce lls ex pressing T ce ll receptor Vf38 reached a peak level on day 2 after SEB treatment. In co nclusion, we demonstr ated th e ill vivo DC response to SEB in the mouse spleen, especiall y a potent stimul ati ve effect of SEB on DCs in vivo, a temporal distribution pattern of DCs as well as T cells incl uding TCR Vf38+ T ce lls, and a differenti al expression pattern of costimul atory molecules on the acti va ted DCs. The results of the present study indicate that DCs are the principal type of APCs which mediate T cell activation by SAg ill vivo, and that each costimulatory molecule may have diffe rent role in the activation of DCs by SAg. Thus, it is plausible to speculate that DCs playa critical role in the T cell clonal expansion by SAgs and other SAg-induced immune responses ill vivo.