Open AccessCritical role of the Th1/Tc1 circuit for the generation of tumor‐specific CTL during tumor eradication in vivo by Th1‐cell therapy
Author(s) -
Chamoto Kenji,
Kosaka Akemi,
Tsuji Takemasa,
Matsuzaki Junko,
Sato Takeshi,
Takeshima Tsuguhide,
Iwakabe Kenji,
Togashi Yuji,
Koda Toshiaki,
Nishimura Takashi
Publication year - 2003
Publication title -
cancer science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 1347-9032
DOI - 10.1111/j.1349-7006.2003.tb01377.x
Subject(s) - cell therapy , in vivo , cancer research , chemoimmunotherapy , cytotoxic t cell , ctl* , spleen , immunotherapy , adoptive cell transfer , cell , immunology , cd8 , medicine , biology , antigen , t cell , immune system , in vitro , biochemistry , genetics , microbiology and biotechnology
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 restimulated with the model tumor antigen (OVA) for 4 days. Spleen cells obtained from mice cured by Th1‐cell therapy produced high levels of IFN‐γ, 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‐γ‐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 chemoimmuno‐therapy 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.