title: An essential role of antigen-presenting cell/T-helper type 1 cell-cell interactions in draining lymph node during complete eradication of class II-negative tumor tissue by T-helper type 1 cell therapy.
abstract: Prior studies have shown that transfer of ovalbumin (OVA)-specific T helper type 1 (Th1) cells into mice bearing MHC class II+ OVA-expressing tumor cells (A20-OVA) causes complete tumor rejection. Here we show that, although Th1 cell therapy alone was not effective against MHC class II- OVA-expressing tumor cells (EG-7), treatment of mice bearing established EG-7 tumors by i.v. transfer of Th1 cells combined with i.t. injection of the model tumor antigen OVA induced complete tumor rejection. Transferred Th1 cells enhanced the migration of tumor-infiltrating antigen-presenting cells (APC) that had processed OVA into the draining lymph node (DLN). Although transferred Th1 cells were randomly distributed in DLN, distal LN, spleen, and tumor tissue, active proliferation of Th1 cells always initiated in DLN, where Th1 cells efficiently interacted with APC that presented OVA. In parallel, OVA-tetramer+ CTLs, showing EG-7-specific cytotoxicity, were highly induced in DLN and the local tumor site. The OVA-tetramer+ CTL functioned systemically because two bilateral tumor masses were both completely rejected on treatment of one tumor. Furthermore, either active proliferation of transferred Th1 cells or generation of tetramer+ CTL was not induced in MHC class II-deficient mice and LN-deficient Aly/Aly mice. These results indicate that DLN is an indispensable organ for initiating active APC/Th1 cell interactions, which is critical for inducing complete eradication of tumor mass by tumor-specific CTL.
authors.affiliation: Division of Immunoregulation, Section of Disease Control, Institute for Genetic Medicine, Hokkaido University, Sapporo 060-0815, Japan.
authors.forename: Kenji
authors.initials: K
authors.lastname: Chamoto
authors.forename: Daiko
authors.initials: D
authors.lastname: Wakita
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Narita
authors.forename: Yue
authors.initials: Y
authors.lastname: Zhang
authors.forename: Daisuke
authors.initials: D
authors.lastname: Noguchi
authors.forename: Hideaki
authors.initials: H
authors.lastname: Ohnishi
authors.forename: Takeshi
authors.initials: T
authors.lastname: Iguchi
authors.forename: Tomoaki
authors.initials: T
authors.lastname: Sakai
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Ikeda
authors.forename: Takashi
authors.initials: T
authors.lastname: Nishimura
mesh_terms: D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology* / Q000473:pathology; D000951:Antigens, Neoplasm / Q000276:immunology / Q000378:metabolism; D002450:Cell Communication / Q000276:immunology*; D002465:Cell Movement / Q000276:immunology; D000949:Histocompatibility Antigens Class II / Q000276:immunology*; D016219:Immunotherapy, Adoptive / Q000379:methods*; D008198:Lymph Nodes / Q000276:immunology* / Q000473:pathology; D008213:Lymphocyte Activation; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D010047:Ovalbumin / Q000235:genetics / Q000276:immunology / Q000494:pharmacology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology* / Q000473:pathology; D013945:Thymoma / Q000235:genetics / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D013953:Thymus Neoplasms / Q000235:genetics / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D014162:Transfection
chemical_list: D000951:Antigens, Neoplasm; D000949:Histocompatibility Antigens Class II; D010047:Ovalbumin