Abstract
Immunization with inactivated autoreactive T cells may induce idiotype anti-idiotypic reactions to deplete autoreactive T cells, which are involved in autoimmune diseases. However, it is unknown whether attenuated activated healthy autologous T-cell immunization could increase anti-tumor immune responses. To this end, C57Bl/6 mice were immunized with attenuated activated autologous T cells. The splenocytes from immunized mice showed a higher proliferative ability than that from naive mice. The special phenotype analysis showed that there were more CD8+ T cells and CD62L+ T cells in immunized mice after 24 h of culture with 10% fetal calf serum complete medium in vitro (P<0.01). These results demonstrated that this immunization may activate T cells in vivo. Furthermore, the splenocytes from immunized mice revealed resistance to activation-induced cell death (AICD) in vitro. To further study the relative genes that are responsible for the higher proliferation and resistance to AICD, the expression of Fas/Fas ligand (FasL) and GADD45b was measured by real-time PCR. The results indicated that GADD45β transcription was higher in the splenocytes from immunized mice than that in the naive mice. In addition, the Fas expression showed a parallel higher, but FasL did not change obviously. To investigate the biologic functions induced by immunization in vivo, a tumor model was established by EL-4 tumor cell inoculation in C57/Bl mice. Mice receiving autologous T-cell immunization had significantly inhibited tumor growth in vivo (P<0.01). This study implicated that immunization with attenuated activated autologous T cells enhances anti-tumor immune responses that participate in tumor growth inhibition.
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Acknowledgements
This work was supported by Science and Technology Commission of Shanghai Municipality (Nos. 03DJ14009, 04DZ14902, 05ZR14055, 054319928), Shanghai Municipal Education (No. 05BZ26) and Shanghai Leading Academic Discipline Project (T0206), Translational Research Seed Fund of Institute of Health Sciences (No. XK2172).
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Wang, L., Du, F., Cao, Q. et al. Immunization with autologous T cells enhances in vivo anti-tumor immune responses accompanied by up-regulation of GADD45β. Cell Res 16, 702–712 (2006). https://doi.org/10.1038/sj.cr.7310083
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DOI: https://doi.org/10.1038/sj.cr.7310083
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