Immunization with autologous T cells enhances in vivo anti-tumor immune responses accompanied by up-regulation of GADD45beta

Cell Res. 2006 Aug;16(8):702-12. doi: 10.1038/sj.cr.7310083.

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 GADD45beta 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens, Differentiation / genetics
  • Antigens, Differentiation / metabolism*
  • Antineoplastic Agents / immunology*
  • Cell Death
  • Cell Proliferation
  • Fas Ligand Protein / metabolism
  • Female
  • Humans
  • Immunization*
  • Interleukin-12 / immunology
  • Killer Cells, Natural / immunology
  • Lymphocyte Activation
  • Mice
  • Mice, Inbred C57BL
  • Neoplasms / immunology*
  • T-Lymphocytes / cytology
  • T-Lymphocytes / immunology*
  • T-Lymphocytes / physiology
  • T-Lymphocytes / radiation effects
  • Transplantation, Autologous*
  • Up-Regulation*
  • fas Receptor / metabolism

Substances

  • Antigens, Differentiation
  • Antineoplastic Agents
  • Fas Ligand Protein
  • Gadd45b protein, mouse
  • fas Receptor
  • Interleukin-12