BACKGROUND Human CD1 has recently emerged as a third family of antigen-presenting molecules that is distinct from either major histocompatibility complex class I or class II. OBJECTIVE We investigated whether the CD1b-restricted T-cell interaction with antigen alters human IgG subclass and IgE isotype production. METHODS CD1b-restricted antigen-specific T cells derived from the skin lesion of a patient with leprosy were stimulated with their cognate antigen, lipoarabinomman (LAM) of Mycobacterium leprae, in the presence of CD1+ antigen-presenting cells and tested for their ability to alter IgG subclass and IgE production from IgD+ B cells. RESULTS CD1-restricted T cells cultured with CD1+ antigen-presenting cells in the absence of LAM induced IgG1, IgG3, IgG4, and IgE, whereas CD1b-restricted T cells cultured in the presence of LAM induced IgG1 and IgG3 and inhibited production of IgG4 and IgE. Production of IgG4 and IgE was rescued in the CD1-restricted system by the addition of anti-interferon-gamma. IgG2 production was not induced under any circumstances. CONCLUSIONS In this study we demonstrated that a specific CD1b-restricted T-cell line can behave similarly to classically-restricted Th1-type T cells. CD1b-restricted T-cells of this type may regulate immune responses to microbial pathogens by simultaneously enhancing cell-mediated immunity and downregulating IgG4 and IgE responses.