Primary antitumor immune response mediated by CD4+ T cells

Immunity. 2005 Mar;22(3):371-83. doi: 10.1016/j.immuni.2005.02.003.


Gene-targeted mice have recently revealed a role for lymphocytes and interferon-gamma (IFNgamma) in conferring protection against cancer, but the mechanisms remain unclear. Here, we have characterized a successful primary antitumor immune response initiated by naive CD4+ T cells. Major histocompatibility complex class II (MHC-II)-negative myeloma cells injected subcutaneously into syngeneic mice were surrounded within 3 days by macrophages that captured tumor antigens. Within 6 days, naive myeloma-specific CD4+ T cells became activated in draining lymph nodes and subsequently migrated to the incipient tumor site. Upon recognition of tumor-derived antigenic peptides presented on MHC-II by macrophages, the myeloma-specific CD4+ T cells were reactivated and started to secrete cytokines. T cell-derived IFNgamma activated macrophages in close proximity to the tumor cells. Tumor cell growth was completely inhibited by such locally activated macrophages. These data indicate a mechanism for immunosurveillance of MHC-II-negative cancer cells by tumor-specific CD4+ T cells through collaboration with macrophages.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • CD4-Positive T-Lymphocytes / immunology*
  • Cell Line, Tumor
  • Collagen
  • Drug Combinations
  • Drug Therapy
  • Enzyme-Linked Immunosorbent Assay
  • Flow Cytometry
  • Histocompatibility Antigens Class II / immunology
  • Immunohistochemistry
  • Immunologic Surveillance*
  • Interferon-gamma / immunology
  • Interferon-gamma / metabolism
  • Laminin
  • Lymphocyte Activation / immunology*
  • Macrophages / immunology
  • Mice
  • Mice, SCID
  • Mice, Transgenic
  • Multiple Myeloma / immunology*
  • Neoplasm Transplantation
  • Proteoglycans
  • Receptors, Antigen, T-Cell / genetics


  • Drug Combinations
  • Histocompatibility Antigens Class II
  • Laminin
  • Proteoglycans
  • Receptors, Antigen, T-Cell
  • matrigel
  • Interferon-gamma
  • Collagen