Critical role of the Th1/Tc1 circuit for the generation of tumor-specific CTL during tumor eradication in vivo by Th1-cell therapy.

Abstract

Th1 and Th2 cells obtained from OVA-specific T cell receptor transgenic mice completely eradicated the tumor mass when transferred into mice bearing A20-OVA tumor cells expressing OVA as a model tumor antigen. To elucidate the role of Tc1 or Tc2 cells during tumor eradication by Th1- or Th2-cell therapy, spleen cells obtained from mice cured of tumor by the therapy were re-stimulated with the model tumor antigen (OVA) for 4 days. Spleen cells obtained from mice cured by Th1-cell therapy produced high levels of IFN-gamma, while spleen cells from mice cured by Th2-cell therapy produced high levels of IL-4. Intracellular staining analysis demonstrated that a high frequency of IFN-gamma-producing Tc1 cells was induced in mice given Th1-cell therapy. In contrast, IL-4-producing Tc2 cells were mainly induced in mice after Th2-cell therapy. Moreover, Tc1, but not Tc2, exhibited a tumor-specific cytotoxicity against A20-OVA but not against CMS-7 fibrosarcoma. Thus, immunological memory essential for CTL generation was induced by the Th1/Tc1 circuit, but not by the Th2/Tc2 circuit. We also demonstrated that Th1-cell therapy is greatly augmented by combination therapy with cyclophosphamide treatment. This finding indicated that adoptive chemoimmunotherapy using Th1 cells should be applicable as a novel tool to enhance the Th1/Tc1 circuit, which is beneficial for inducing tumor eradication in vivo.

• Authors: Kenji Chamoto, Akemi Kosaka, Takemasa Tsuji, Junko Matsuzaki, Takeshi Sato, Tsuguhide Takeshima, Kenji Iwakabe, Yuji Togashi, Toshiaki Koda, Takashi Nishimura
• Journal: Cancer science (Cancer Sci) Vol. 94 Issue 10 Pg. 924-8 (Oct 2003) ISSN: 1347-9032 [Print] England
• PMID: 14556668 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Interleukin-4
• Interferon-gamma

Topics

• Animals
• CD8-Positive T-Lymphocytes (cytology, immunology)
• Cell- and Tissue-Based Therapy (methods)
• Cells, Cultured
• Flow Cytometry
• Immunotherapy, Adoptive (methods)
• Interferon-gamma (metabolism)
• Interleukin-4 (metabolism)
• Mice
• Mice, Inbred BALB C
• Mice, Transgenic
• Neoplasm Transplantation
• Neoplasms (immunology, pathology)
• Spleen (cytology)
• Survival Rate
• Th1 Cells (immunology, transplantation)
• Th2 Cells (immunology, transplantation)