T Helper Cytokine Responses Induced by Nasal Immunization with Glucosyltransferase-I of Streptococcus sobrinus

Abstract

Our previous study showed that nasal immunization with glucosyltransferase-I (GTF-I) produced by Streptococcus sobrinus elicits serum IgG, serum IgA, and salivary IgA antibody responses that provide protection against dental caries caused by S. sobrinus infection. In this study, to develop an effective vaccine for the prevention of dental caries, we assessed T helper (Th) cell responses in systemic and mucosal compartments when GTF-I was administered nasally. When CD4+ T cells isolated from the spleen or cervical lymph nodes of mice immunized with GTF-I alone or GTF-I plus unmethylated cytosine-phosphate-guanine oligodeoxynucleotides (CpG ODN) were re-stimulated with GTF-I in vitro, significant levels of proliferative responses were induced. Analysis of Th1 (IFN-γ) and Th2 (IL-4) cytokine responses showed that GTF-I-specific Th cells from mice given GTF-I alone produced a significant level of IL-4 with low IFN-γ. On the other hand, CD4+ T cells from mice given GTF-I plus CpG ODN produced increased levels of IFN-γ when compared with those of mice given GTF-I alone, whereas the IL-4 production was not changed. The IgG subclass responses confirmed the cytokine profile, showing that while nasal GTF-I elicited mainly IgG1 antibodies, GTF-I plus CpG ODN further enhanced IgG2a and IgG2b, but not IgG1, antibody responses. These results suggest that nasal immunization with GTF-I elicits GTF-I-specific Th2 cytokine responses in both mucosal and systemic lymphoid tissues and that CpG ODN as an adjuvant enhances Th1-type cytokine responses to co-administered GTF-I.