Immunization with autologous T cells enhances in vivo anti-tumor immune responses accompanied by up-regulation of GADD45beta.
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.
Wang
Li
L
Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Du
Fang
F
Cao
Qi
Q
Sheng
Huiming
H
Shen
Baihua
B
Zhang
Yan
Y
Diao
Yingna
Y
Zhang
Jingwu
J
Li
Ningli
N
D000818:Animals; D000943:Antigens, Differentiation / Q000235:genetics / Q000378:metabolism*; D000970:Antineoplastic Agents / Q000276:immunology*; D016923:Cell Death; D049109:Cell Proliferation; D053222:Fas Ligand Protein / Q000378:metabolism; D005260:Female; D006801:Humans; D007114:Immunization; D018664:Interleukin-12 / Q000276:immunology; D007694:Killer Cells, Natural / Q000276:immunology; D008213:Lymphocyte Activation; D051379:Mice; D008810:Mice, Inbred C57BL; D009369:Neoplasms / Q000276:immunology*; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000502:physiology / Q000528:radiation effects; D014182:Transplantation, Autologous; D015854:Up-Regulation; D019014:fas Receptor / Q000378:metabolism; D000097642:GADD45 Proteins
D000943:Antigens, Differentiation; D000970:Antineoplastic Agents; D053222:Fas Ligand Protein; D018664:Interleukin-12; D019014:fas Receptor; C490125:Gadd45b protein, mouse; D000097642:GADD45 Proteins