Activated eosinophils are the major source of Th2-associated cytokines in the schistosome granuloma

Eosinophils are a numerically dominant cell population within the schistoso me granuloma, These granuloma eosinophils can produce a variety of cytokine s, including IL-2, IL-4, IL-5, and IFN-gamma, Therefore, eosinophils may pl ay a key role in the determination of the unique cytokine microenvironment within the granuloma milieu. These studies investigated the potential role of eosinophils in the regulation of granuloma immunopathology, We have char acterized spleen- and granuloma-derived eosinophils based on cellular activ ation and cytokine production during the development of murine schistosomia sis. Based on the criteria of hypodensity and CD69 expression, granuloma eo sinophils were highly activated and very homogeneous at 7 and 11 wk postinf ection. Splenic eosinophils were also activated at 7 wk postinfection, but were much more heterogeneous than their granuloma counterparts. By 11 wk po stinfection, few hypodense splenic eosinophils were observed. Eosinophils r epresented the majority of cytokine-producing cells in the granuloma and we re a dominant source of IL-4, Eosinophils also produced IL-2, IL-5, and IFN -gamma, using the criteria of mRNA in situ hybridization and intracellular cytokine staining by FAGS. Granuloma eosinophil activation and cytokine pro duction were greatest at the time of maximum granuloma formation, i.e., 10- 12 wk after initial cercarial exposure. Therefore, locally activated eosino phils, not Th2 lymphocytes, produce the majority of Th2 cytokines in the gr anuloma milieu and may be important determinators of immunopathology in sch istosomiasis.