Outer membrane protein with a 53-kDa molecular weight (Ag53) isolated from Porphyromonas gingivalis evokes strong humoral immune responses in many periodontitis patients. To examine the effects of cytokines produced by Ag53-specific Th cells on the IgG production against Ag53, we established Ag53-specific Th-cell lines from patients with early onset periodontitis and from healthy volunteers. We then developed a mixed lymphocyte culture system between Ag53-specific Th cells and auto- or allo-derived T-cell-depleted leukocytes produced from the subjects whose HLA class II haplotypes were completely matched. Interferon-gamma production was observed in all Th cell lines from patients and healthy subjects. As for Th2 type cytokines, interleukin (IL)-4, IL-5, IL-6 and IL-10 production varied greatly in Th cells regardless of the periodontal condition of the donor. Only Th cell lines with a high Th2/Th1 ratio induced Ag53-specific IgG production when cocultured with T-cell-depleted leukocytes. Thus, the difference in Th2/Th1 balance may regulate the Ag53-specific IgG production.