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Sensitized CD4 - T cells in peripheral lymphoid tissues after exposure to the pathogen antigen, can be divided into Th1 and Th2 two categories, the CD4 to effect T cell. Th1 cells secrete IL-2, IFN-γ and TNF-beta and other cytokines involved in the cytotoxic T cells (CTL)-mediated cellular immunity, mainly in the anti-cell infection (such as viral infections, tuberculosis mycobacterial infection, etc. ) play an important role; whereas Th2 cells secreted IL-4, IL-5, IL-6, IL-10 and IL-13 and other cytokines, and its main function is to stimulate B cell proliferation and activation of eosinophils, and promote antibody (IgG1 and IgE), plays a major role in the immune response involved in humoral immunity, anti-cell infection caused by allergens. Schistosomiasis is a typical drift and polarization occurs in different stages of infection, having a Th1, Th2 immune responses advantage chronic infection. In the the schistosomiasis infection process, the host immune response can be roughly divided into three stages. Mouse infection model, for example, infected with Schistosoma japonicum infection of about 21 to 25 days (3 to 3.5 weeks), a Th1-type immune response, mainly by the cercariae, Schistosomula and adult non-egg antigen induced . Starting from about 26 to 28 days (3.5 to 4 weeks), adults began to lay eggs about 35 days (5 weeks) cytokine environment shifts from the advantages of Th1 response gradually to offset the advantages of Th2 response. To 56 days (8 weeks), the body was being transferred to the egg antigen-induced Th2 response advantages. Approximately 91 days (13 weeks) of infection, the infection into the chronic phase, the Th1, Th2 immune responses are maintained at not too high plateau, but still Th2-type immune response dominant. Many factors affect Th1/Th2 response polarization direction, including: dose and form of the antigen, the antigen peptide and TCR affinity, antigen presenting cells (APC) type of costimulatory molecules and cytokines in. In recent years, studies have found that Th1, Th2 cells have different sensitivity to TCR-induced apoptosis (TCR-ICD), but different antigens of the pathogen in different stages of infection by inducing Th cell apoptosis thus affecting Th1/Th2 polarization. In the present study, we first established schistosome infected mice (mice infected with body meat non eggs and egg antigen) and infection associated with artesunate ester (Artesunate) chemotherapy mice (infected mice does not contain insects egg antigen) model, flow cytometry, dynamic observation 23,35,56 days after infection mice Th1 and Th2 cells apoptosis key molecule caspase-3 level changes, followed by detection of the SWA, SEA immunized mice Th1, Th2 cells, the level of caspase-3 and the the normal CD4 ~~ T cells in vitro SWA, SEA stimulated production of IFN-gamma and IL-4 intracellular caspase-3 levels change, the last in the SWA SEA mice immunized with SWA SEA in vitro re-stimulation the mouse mononuclear lymphocytes while adding an inhibitor of caspase or GrB, Th1, Th2 cell apoptosis was detected by TUNEL assay. In this study, the following main results: 1. During natural infection, infection 23 days mice showed a Th1 type response, the proportion of Th2 cells apoptosis (10.16%) was significantly higher than Th1 cells (6.77%). 35 days of infection, schistosomiasis adult spawning, mice cytokine environment is experiencing a shift in Th1, Th2 responses are enhanced at the same time, from the advantages of Th1 response gradually to offset the advantages of Th2 response (Th2 cytokines gradual increase in Th1 cytokines), this time, the proportion of mice Th1 cell apoptosis (7.60%), however, the proportion of Th2 cell apoptosis (5.95%). To the infection of 56 days in vivo immune response in mice eggs antigen-induced Th2-type immune response of Th1 apoptosis ratio continues to increase (9.66%), while the proportion of Th2 cells apoptosis with infection at day 35 No obvious change ( 6.18%). Mice 23 days after infection combined with chemotherapy mainly Th1 type immune response Th2 cells in vivo apoptosis (11.72%) was significantly higher than Th1 cell apoptosis (6.89%), consistent with the infection 23 days in mice results. Infection 35 days mice exist egg antigen 35 days mice egg antigen, and infection associated with chemotherapy, the proportion of Th1 cells in vivo apoptosis of infected mice (7.60%) than infection associated with chemotherapy mice ( 4.58%), the proportion of apoptosis of Th2 cells, infection group (5.95%) than the the infection combination chemotherapy group (11.70%) low. As the infection time, infection 56 days immune response mainly for egg antigen-induced Th2 response advantages, infected mice Th1 cell apoptosis (9.66%) and infection combined with chemotherapy in mice (5.61%) , suggesting that the former in the body can be stronger Th1 cells induced apoptosis. It is reasoned that Schistosoma japonicum infection early, non-egg antigen may be advantage-induced apoptosis of Th2 cells, and thus more conducive to the formation of Th1 polarization; oviposition, egg antigen-induced apoptosis of Th1 cells may advantage, and thus more conducive to the formation of Th2 polarization. Schistosome after natural infection combined with SWA, SEA in vitro antigenic stimulation, this phenomenon is even more obvious: the Th cell infection 23 days, SWA in vitro stimulation, Th2 cell apoptosis (17.69%) was significantly higher than Th1 cells (13.33%). 23 days of infection associated with chemotherapy, the proportion of Th2 cell apoptosis (19.41%) was significantly higher than the Th1 cell apoptosis (12.88%). Infection 35 days after the schistosome eggs, plus SEA in vitro stimulation, Th2 cell apoptosis (14.79%) is still slightly higher than Th1 cells (12.24%). Infection 56 days after the combination of in vitro SEA stimulation of Th1 cell apoptosis (14.78%) was significantly higher than that of Th2 cells apoptosis (10.41%). In vitro addition of SEA antigen stimulation, infection and infection associated with chemotherapy, 35 days of infection in vivo apoptosis of Th1 cells (12.24%) was significantly higher than infection associated with chemotherapy Th1 cell apoptosis (7.58%); infection Th2 apoptosis combined with chemotherapy 35 days (15.73%) is slightly higher than the the infected group Th2 cell apoptosis (14.79%). Infection 56 days mice Th1 apoptosis (14.78%) infection the combined chemotherapy Th1 apoptosis (6.80%) compared to the more obvious increased; Th2 cell apoptosis (10.41%) lower than the infection combination chemotherapy group, the proportion of Th2 apoptosis (13.51%). Further evidence of non-egg antigen egg antigen-induced the Th1/Th2 apoptosis tendency, respectively SWA Sea immunization of normal mice were observed to the SWA immune mice, Th2 cells apoptosis rate (12.27%) Th1 cells was significantly higher than the percentage of apoptotic (6.64%); SEA immunized mice, Th1 cell apoptosis (8.34%) was significantly higher than the proportion of Th2 cells apoptosis (6.99%) with magnetic beads elected to normal mouse CD4 - T cells, SWA, SEA, respectively vitro stimulation of detected two cell apoptosis, Similarly, this experiment also support our view. 2 mononuclear lymphocytes stimulate SWA or SEA immunity of mice with SWA, SEA, and then were added to GrB inhibitor Z-AAD-CMK or caspase inhibitor Z-VAD-FMK, followed by TUNEL assay Th1 , Th2 cell apoptosis. The results show that the the SWAP induction of Th2 apoptosis may be partially GrB inhibitor blocking SEA induction of the apoptosis of Th1 cells can be partially blocked caspase inhibitor. Different antigen-induced Th cell apoptosis seen in the process of schistosomiasis infection may also its priority activated Th1 and Th2 cells apoptosis pathway. In summary, the present study, we found that schistosomiasis in the early stages of infection, the non-egg antigen seems to be more Th2 cells induced apoptosis which is conducive to the formation of Th1 polarization; After spawning, egg antigen may be more Ease of Th1 cells induced apoptosis, which is conducive to the formation of Th2 polarization. We also explore the possible mechanisms underlying this phenomenon, non-egg antigen may be through the GrB apoptosis channels advantages induced apoptosis of Th2 cells and thus participate in Th1 polarization; egg antigen may be advantages through the caspase pathway of apoptosis induced apoptosis of Th1 cells and thus participate in the Th2 polarization. These results suggest that pathogen antigen may be different strengths in different stages of infection the tendency induced Th1/Th2 cell apoptosis, thus contributing to the achievement of the Th1/Th2 type conversion, in order to achieve their immune evasion and chronic infection.
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