CpG oligonucleotides can prophylactically immunize against Th2-mediated schistosome egg-induced pathology by an IL-12-independent mechanism

Using a Schistosoma mansoni egg-induced granuloma model, we examined the ab ility of CpG oligodeoxynucleotides (ODN) to suppress Th2-type cytokine expr ession and to prophylactically immunize against Th2-dependent pulmonary pat hology. The mechanism was examined by studying Th2 response regulation in c ytokine-deficient mice. Surprisingly, our findings revealed several functio ns of CpG DNA that were completely IL-12 independent. Most striking was the marked suppression in Th2 cytokine expression and granulomatous inflammati on observed in eeg/CpG-sensitized IL-12-deficient mice. Immune deviation wa s not dependent on NK or B cells. However, a role for IL-10, B7.1, and CD40 expression in Th2 response inhibition was suggested. Indeed, CpG ODN up-re gulated all three elements in both wild-type and IL-12-deficient mice. The role of IL-10 was demonstrated in mice exhibiting combined deficiencies in IL-12 and IL-10, Here, a marked increase in egg-specific IL-4/IL-5-producin g cells confirmed a role for both cytokines in Th2 response inhibition. Nev ertheless, the frequency of Th2-producing cells was again reduced by CpG OD N, However, in marked contrast to IL-12-deficient animals, a significant in crease in IFN-gamma-producing cells likely explains the reduced Th2 respons e in IL-10/IL-12-deficient mice. Thus, a novel IL-12-independent type 1-ind ucing pathway was revealed in the combined absence of IL-12 and IL-10, Toge ther, these data demonstrate 1) that the Th1-promoting activity of CpG DNA is controlled by IL-12 and IL-10, and 2) that Th2 response inhibition by Cp G ODN involves IL-12-independent changes in IL-10 and costimulatory molecul e expression. These findings illustrate the utility of CpG DNA as adjuvants for vaccines designed to prevent Th2-dependent immunopathology.