B7-2 REQUIREMENT FOR HELMINTH-INDUCED GRANULOMA-FORMATION AND CD4 TYPE-2 T-HELPER CELL CYTOKINE EXPRESSION

B7 ligands on APCs engage CD28/CTLA4 counter-receptors on T cells crit ical for T lymphocyte activation and functional differentiation of T h elper subsets. To examine whether the ligands B7-1 (CD80) and B7-2 (CD 86) affect gene expression of Th2 cytokines and development of Th2-med iated pathologic tissue reactions, mice were treated with anti-B7-1 or anti-B7-2 at the time of sensitization to footpad inoculation of Schi stosoma mansoni eggs or induction of pulmonary granuloma by i.v. injec ted eggs, Anti-B7-2 treatment inhibited pulmonary granuloma formation by 74% and decreased levels of lung IL-5 and IL-13 transcripts compare d with those in animals given control Ig by 20- and 5-fold, respective ly, while anti-B7-1 administration has no effect. Anti-B7-2 treatment blocked CD4 cell gene expression of IL-4, IL-5, and IL-13, but had no effect on INF-gamma or IL-10 in animals inoculated with S. mansoni ova , larvae from the filarial helminth Brugia malayi, or CFA. Anti-B7-1 a dministration had no effect on CD4 cell transcript levels of IL-4 and IL-5, but inhibited IFN-gamma in mice inoculated with ova. Similar eff ects of anti-B7-2 on CD4 cell cytokine expression were observed in IL- 4 knockout mice, indicating the existence of an alternative pathway fo r induction and/or expression of these cytokine genes, These findings suggest a possible role for anti-B7-2 in the therapy of infectious and atopic diseases in which immunopathologic reactions are mediated by s elected Th2 cytokines.