Chronic pulpal inflammation under caries appears to be elicited by bacterial antigens that diffuse into the pulp through dentinal tubules. This prompted the hypothesis that cytokines elicited by antigens from Streptococcus mutans, which frequently dominates shallow lesions, could play a major role in eliciting the initial T-cell response in the pulp. To test this, we examined the ability of S. mutans to stimulate T cells and elicit cytokines and used Lactobacillus casei, which often predominates in deep carious lesions where B cells and plasma cells predominate, as a control. In addition, the presence of cytokines in the pulp was analyzed at the mRNA level. S. mutans elicited potent gamma interferon (IFN-␥) responses in peripheral blood mononuclear cell cultures and reduced the CD4/CD8 ratio by promoting CD8 ؉ T cells. Multiple inflammatory cytokine mRNAs (IFN-␥, interleukin 4 [IL-4], and IL-10) were detected in human dental pulp. A higher prevalence of IFN-␥ (67%) than IL-4 (19%) or IL-10 (29%) was obtained in shallow caries, suggesting a type 1 cytokine mechanism in early pulpitis where S. mutans predominates. In contrast, in deep caries no differences in cytokine frequency were observed. Furthermore, the presence of IFN-␥ in the pulp correlated with the presence of S. mutans. The extraordinary induction of type 1 cytokines and the preferential activation of CD8 ؉ T cells by S. mutans offers an explanation for the etiology of the CD8 ؉ T-cell-dominant lesion in early pulpitis and suggests that S. mutans may have a major impact on the initial lesion and pulpal pathology.Although the dental pulp is equipped with cells of the immune system (16), the immune response in the pulp to caries pathogens is poorly understood. A chronic pulpal inflammation under caries is likely elicited by bacterial antigens that diffuse into the pulp through dentinal tubules (2,3,14). Immunohistological studies of dental pulps under shallow caries have revealed a lesion that is restricted almost exclusively to T cells, with CD8 ϩ T cells predominating (9, 14). As the carious lesion enlarges and invades the inflamed dental pulp, CD8 ϩ T cells continue to dominate but CD4 ϩ T cells, B cells, and plasma cells appear in substantial numbers (9,14). We are interested in understanding why the immune cell types shift during caries progression. We reasoned that antigens associated with the caries pathogens may preferentially elicit different immune cell types during caries invasion. The dominant organisms in the lesions, which likely elicit host responses, shift from Streptococcus mutans in shallow caries to Lactobacillus casei in deep carious lesions.A type 1 cytokine response is defined as promoting cellmediated response, with gamma interferon (IFN-␥) as the prototypic cytokine and a clear association with interleukin 2 (IL-2), tumor necrosis factor beta, and IL-12. A type 2 response is characterized as promoting one or more B-cell activities, with IL-4 as the prototypic cytokine and an association with IL-5, IL-6, IL-10, and IL-13 (18). This ...