Immunization with autologous T cells enhances in vivo anti-tumor immune responses accompanied by up-regulation of GADD45β

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 GADD45b 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.

Downregulation of CD4+CD25+ regulatory T cells may underlie enhanced Th1 immunity caused by immunization with activated autologous T cells

“…The serum samples were tested in duplicate for the production of IFNγ, IL-12, TNFα and IL-10 using ELISA kits (R&D). In this assay, the IL-12 level was significantly increased in the immunized mice as we reported before (p = 0.0057) [35]. Th1 cytokines IFNγ and TNFα increased significantly also in immunized mice than those from naïve mice (p = 0.047 and 0.021 respectively).…”

“…In our previous work, we reported that administration with irradiated, activated autologous T cells in mice evokes anti-tumor immunity by enhancing the survival of activating T cells, which is accompanied by GADD45b upregulation in T cells [35]. In this report, we further investigated the anti-tumor mechanisms elicited by activated autologous T immunization.…”

“…The purity of T cells obtained from culture was greater than 92%. Purified T cells were irradiated at 3 000 rad, and mice were administrated for immunization as described in our previous report [35].…”

Dying T lymphocytes call for the death of tumor cells

“…Currently, alternative strategies potentially leading to cancer eradication or regression in animal or clinical models are being enthusiastically pursued. In this issue of Cell Research, Wang et al report a novel way to induce tumor immunity by the use of irradiated autologous T cells [5].In their protocol, Wang et al isolated activated T cells from C57BL/6 mouse splenocytes stimulated in vitro. These cells were then irradiated at 30 Gy and injected intraperitoneally into syngeneic mice every 5 days.…”

“…Currently, alternative strategies potentially leading to cancer eradication or regression in animal or clinical models are being enthusiastically pursued. In this issue of Cell Research, Wang et al report a novel way to induce tumor immunity by the use of irradiated autologous T cells [5].…”