TY - JOUR
T1 - Critical role of the Th1/Tc1 circuit for the generation of tumor-specific CTL during tumor eradication in vivo by Th1-cell therapy
AU - Chamoto, Kenji
AU - Kosaka, Akemi
AU - Tsuji, Takemasa
AU - Matsuzaki, Junko
AU - Sato, Takeshi
AU - Takeshima, Tsuguhide
AU - Iwakabe, Kenji
AU - Togashi, Yuji
AU - Koda, Toshiaki
AU - Nishimura, Takashi
N1 - Copyright:
Copyright 2016 Elsevier B.V., All rights reserved.
PY - 2003/10
Y1 - 2003/10
N2 - 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 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.
AB - 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 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.
UR - http://www.scopus.com/inward/record.url?scp=20244389660&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=20244389660&partnerID=8YFLogxK
U2 - 10.1111/j.1349-7006.2003.tb01377.x
DO - 10.1111/j.1349-7006.2003.tb01377.x
M3 - Article
C2 - 14556668
AN - SCOPUS:20244389660
SN - 1347-9032
VL - 94
SP - 924
EP - 928
JO - Cancer Science
JF - Cancer Science
IS - 10
ER -