Primary antitumor immune response mediated by CD4+ T cells.
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.
Corthay
Alexandre
A
Institute of Immunology, University of Oslo, Rikshospitalet and Rikshospitalet University Hospital, 0027 Oslo, Norway. alexandre.corthay@medisin.uio.no
Skovseth
Dag K
DK
Lundin
Katrin U
KU
Røsjø
Egil
E
Omholt
Hilde
H
Hofgaard
Peter O
PO
Haraldsen
Guttorm
G
Bogen
Bjarne
B
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D045744:Cell Line, Tumor; D003094:Collagen; D004338:Drug Combinations; D004358:Drug Therapy; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D000949:Histocompatibility Antigens Class II / Q000276:immunology; D007150:Immunohistochemistry; D007157:Immunologic Surveillance; D007371:Interferon-gamma / Q000276:immunology / Q000378:metabolism; D007797:Laminin; D008213:Lymphocyte Activation / Q000276:immunology*; D008264:Macrophages / Q000276:immunology; D051379:Mice; D016513:Mice, SCID; D008822:Mice, Transgenic; D009101:Multiple Myeloma / Q000276:immunology*; D009368:Neoplasm Transplantation; D011509:Proteoglycans; D011948:Receptors, Antigen, T-Cell / Q000235:genetics
D004338:Drug Combinations; D000949:Histocompatibility Antigens Class II; D007797:Laminin; D011509:Proteoglycans; D011948:Receptors, Antigen, T-Cell; C059485:matrigel; D007371:Interferon-gamma; D003094:Collagen