Induction of regulatory T cells by Opisthorchis viverrini

Opisthorchis viverrini causes public health problems in South-East Asia. Recently, TGF-β and IL-10 have been reported to increase in O. viverrini-infected hamsters but the sources of these cytokines are still unknown. In this study, the CD4⁺ T cells in infected hamsters were investigated. It was demonstrated that IL-4⁺ CD4⁺ T cells were significantly increased in hamster spleens and mesenteric lymph nodes (MLNs) during chronic infection. Interestingly, IL-10⁺ CD4⁺ T cells were also discovered at a significant level while Treg (T regulatory)-like TGF- β⁺ CD4⁺ T cells were in MLNs of infected hamsters. Moreover, the CD4⁺ CD25⁺ Foxp3⁺ Treg cell response was significantly found both in spleens and MLNs in infected hamsters. The findings were then confirmed by development of T-cell clones against crude somatic antigens (CSAg) in immunized BALB/c mice. Five clones named TCC21, TCC23, TCC35, TCC41 and TCC108 were established. The TCC21 was found to be the TGF-β⁺ CD4⁺ while TCC35, TCC41 and TCC108 were IL-4⁺ CD4⁺ and TCC23 was IFN-γ⁺ CD4⁺ . This TGF-β⁺ CD4⁺ T clone showed an inhibitory function in vitro in mononuclear cell proliferation via TGF-β-mediated mechanisms. This study indicated that O. viverrini-infected hamsters could induce TGF-β⁺ CD4⁺ Treg-like cells. The CSAg-specific Tregs secreted high TGF-β, and limited immune cell proliferation.