Effects of Toll-like receptor 4 on β2-glycoprotein I-induced splenic T cell subsets differentiation

Our previous study demonstrated that beta 2-glycoprotein I (β2GPI) stimulation promotes bone marrow derived dendritic cells (BMDCs) maturation and T cell proliferation in a Toll-like receptor 4 (TLR4) dependent manner. However, β2GPI 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 β2GPI immunized Balb/c, C3H/HeN and C3H/HeJ mice. According to our results, Th2 dominated differentiation was observed in β2GPI 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 β2GPI 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 β2GPI. In addition, we found that β2GPI-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 β2GPI immunization than those received 2 times, suggesting the amplifying effects of anti-β2GPI Ab on β2GPI induced Th2 response. These findings may partly explain the immune imbalance in APS patient through the view angle of T cell differentiation and anti-β2GPI antibody production.