ARTICLES

Cell Research (2006)16: 702-712
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Immunization with autologous T cells enhances in vivo anti-tumor immune responses accompanied by up-regulation of GADD45¦Â

Li Wang, Fang Du, Qi Cao, Huiming Sheng, Baihua Shen, Yan Zhang, Yingna Diao, Jingwu Zhang, Ningli Li,

Correspondence: Ningli Li Tel:+86-21-64453149; Fax:+86-21-63846383; E-mail: ninglixiaoxue57@sjtu.edu.cn; ninglixiaoxue57@yahoo.com.cn Received 6 Mar 2006; revised 18 Apr 2006; accepted 24 Apr 2006; published online 4 Jul 2006

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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 GADD45β 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.

Cell Research (2006) 16:702-712. doi:10.1038/sj.cr.7310083; published online 4 July 2006

Keywords: anti-tumor immunity, immunization, autologous T cells, GADD45β, AICD