Expression Of PD-1-PDL Induced By Immunization With SEA And SMWA Of Schistosoma Japonicum In Mice

The function of immune system can be defined as immune defence, immunological homeostasis and immunologic surveillance. The immunological mechanism of anti-infection includes innate immunity and adaptive immunity. The main purpose of the immune response to infection is eradication of pathogens; the process can be divided into antigens recognition, activation and differentiation of immunocytes, scavenging of pathogens by effector molecules and effector cells. The termination of the immune response is elimination of the pathogen, but pathogen has versatile impact on immune system which contains enchance or degrades immunological function: low production of specific antibodies by T cells, attenuation of cell immunity and delayed hypersensitivity, reduction of specific lympholeukocyte subset and functional impairment.One of the key features of immune inhibition is negative signals, that can downregulate, or inhibits the immune response. It was recently reported that CTLA-4, PD-1 and BTLA that belong to B7/CD28 families, regulatory T cell and cytokines such as IL-10 take part in the modulation of immune response. Their function is immunological homeostasis, which maintains peripheral T cell tolerance, and protects tissues from autoimmune attack. PD-1 is one of the second negative molecules in B7 superfamilies. The extracellular region of PD-1 consists of a single Ig-like variable (IgV) domain, and the cytoplasmic region contains an immunoreceptor tyrosine-based inhibitory motif. PD-L1 and PD-L2 are ligands for programmed death-1 (PD-1), a member of the CD28/CTLA4 family expressed on activated lymphoid cells, which are expressed on immature dendritic cells (iDC) , mature dendritic cells (mDC) and follicular dendritic cells. Negative signal can be transmitted when PD-1 was combined with its ligands-PD-L1 or PD-L2. The expression of PD-L1 and PD-L2 correlate with secretion of cytokines, PD-L1 and PD-L2 can be stimulated by Th1 cytokines such as IFN-γor Th2 cytokines like IL-4.Immune suppression is a common feature in the parasite infection, i.e Toxoplasma infection can induce high CTLA-4 expression; Filaria malayi infection can suppress T cell proliferation; and African trypanosome infection leads to functional defect of antigen present cells. It was recently reported that he high expression of PD-1 and its ligands correlates with the immune inhibition in microbial and parasitic infections such as the HIV, HCV, Helicobacter pylori, Leishmania mexicana and Schistosoma mansoni. However, there has no report on the relationship between PD-1-PD-L pathway and immune inhibition during Schistosoma japonicum infection. In the present study, we investigated the expression of PD-1-PD-L pathway, and the secretions of relevant cytokines in mice immunized with Schistosoma japonicum antigens.BALB/c mice were immunized 4 times with 50μg soluble egg antigen (SEA) or 50μg soluble male worm antigen (SMWA) of Schistosoma japonicum. 4 weeks after the last immunization, the expression of PD-1, PD-L1 and PD-L2 on splenic cells were measured with flow cytometer, and the secretions of IL-4 and IFN-γin cultural suspension of splenic cells were detected by sandwich-ELISA after the stimulation with ConA. The results showed that the expression ratio of PD-L1, PD-L2 and PD-1 increased after the immunization with two antigens compared with control groups. PD-L2 was much more elevated in SEA immunized mice while PD-L1 was more highly increased with SMWA immunization. Additionally, the expression of both IFN-γand IL-4 in the immunized mice remarked elevated. IFN-γand IL-4 increased more significantly after SMWA and SEA immunization respectively. The up-expression of PD-L1 was correlated with the high secretion of IFN-γand the expression of PD-L2 was correlated with IL-4 secretion. It was firstly reported that the immunization of schistosome antigens can induce the high expression of PD-1-PDL pathway, and the expression of PD-L1 was correlated with the high secretion of IFN-γand the expression of PD-L2 was correlated with IL-4 secretion..