Immune modulation of Th1, Th2, and T-reg transcriptional factors differing from cytokine levels in Schistosoma japonicum infection.

In spite of long-term integrated control programs for Schistosoma japonicum infection in China, the infection is still persistent due to its zoonotic transmission and disease severity which further complicate its control. Th1, Th2, and T-reg cells are involved in S. japonicum immunity; however, their exact roles in immunopathology of this infection are still questionable. Therefore, the monitoring of these T cell subsets' immune responses during a primary infection of S. japonicum at both transcriptional (mRNA) and protein (cytokines) levels would be essential to point out. In experimentally infected white New Zealand rabbits, mRNA expression levels of TBX2, IRF8, GATA3, STAT6, FoxP3, and MAFF were evaluated using qPCR, whereas Th1 (IFN-γ and TNF-α), Th2 (IL4 and IL13), and T-reg (IL10 and TGF-ß1) cytokines were measured by ELISA test. Those parameters were estimated at two phases: the first being 4 and 8 weeks post-infection and the second phase at 12 weeks post-infection. The infected rabbits were categorized into group1 which was treated with praziquantel after the 8th week of infection and group 2 which was left untreated. In the first stage of infection, Th1 was superior to the other types at both mRNA (TBX2 and IRF8) and protein (IFN-γ and TNF-α) levels, but at the late stage, Th2 cytokines (IL4 and IL13) were surprisingly dominated without comparable change in Th2 transcriptional level in group 1. Concisely, the evaluation of T cell transcriptional factors provided clearer evidence about T cellular roles which would be a valuable supplement to control this disease in terms of protective and therapeutic vaccinations.

Effects of Toll-like receptor 4 on ß2-glycoprotein I-induced splenic T cell subsets differentiation.

Our previous study demonstrated that beta 2-glycoprotein I (ß2GPI) stimulation promotes bone marrow derived dendritic cells (BMDCs) maturation and T cell proliferation in a Toll-like receptor 4 (TLR4) dependent manner. However, ß2GPI induced T cell differentiation and the role of TLR4 in this process have rarely been reported. In the present study, we focused on the differentiation of splenic T cells in ß2GPI immunized Balb/c, C3H/HeN and C3H/HeJ mice. According to our results, Th2 dominated differentiation was observed in ß2GPI immunized Balb/c and C3H/HeN mice than in those treated with normal saline (NS), namely the up-regulated levels of Th2 markers GATA3 and IL-4 (p < 0.05). Meanwhile, reduced Th1 markers T-bet and IFN-γ, and Treg marker Foxp3 were observed in ß2GPI immunized mice (p < 0.05). C3H/HeJ mice have the same gene background with C3H/HeN mice except a functional mutant in TLR4 gene. However, the described Th2 differentiation was not detected in these TLR4 deficient mice, indicating the importance of TLR4 in immune response against ß2GPI. In addition, we found that ß2GPI-induced Th2 differentiation could be strengthened by cytokines secreted by dendritic cells (DCs) and DCs-T cells interaction. However, DCs-T cells contact was indispensable during this process because of its unique role in suppressing Th1 function. Furthermore, this Th2 biased differentiation pattern was more noticeable in mice received 4 times ß2GPI immunization than those received 2 times, suggesting the amplifying effects of anti-ß2GPI Ab on ß2GPI induced Th2 response. These findings may partly explain the immune imbalance in APS patient through the view angle of T cell differentiation and anti-ß2GPI antibody production.