CD4+ T-cells from mice immunized to syngeneic sarcomas recognize distinct, non-shared tumor antigens.
We have utilized a newly developed culture system to study the properties of antitumor CD4+ T-cells relevant to the rejection of syngeneic methylcholanthrene sarcomas. Fresh syngeneic dendritic cells prepared from spleen, then pulsed with crude lysates of methylcholanthrene sarcomas, evoke antigen-specific proliferation by CD4+ but not by CD8+ T-cells from tumor-immune mice. Unfractionated splenocytes display similar antigen presenting capacity if they are not irradiated before the pulse with tumor lysate. CD4+ T-cells from mice immunized to individual methylcholanthrene sarcomas proliferate cross-reactively to dendritic cells pulsed with fresh tumor digests, but not to dendritic cells pulsed with cultured tumor cells. This apparent shared recognition of sarcoma lysates was demonstrated to be a result of sensitization to bacterial collagenase during the immunization procedure. Therefore, the murine CD4+ T-cell response to tumor immunization is similar to the CD8+ response in that sensitization occurs predominantly to tumor specific transplantation antigens rather than to shared tumor antigens. Strategies to avoid artefactual tumor cross-recognition by CD4+ T-cells are discussed.
Cohen
P A
PA
Branch of Surgery, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20814.
Cohen
P J
PJ
Rosenberg
S A
SA
Mulé
J J
JJ
D000818:Animals; D017951:Antigen Presentation; D000951:Antigens, Neoplasm / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D016827:CD8 Antigens / Q000032:analysis; D017364:Collagenases / Q000276:immunology; D003429:Cross Reactions; D003713:Dendritic Cells / Q000502:physiology; D005260:Female; D000949:Histocompatibility Antigens Class II / Q000032:analysis; D007114:Immunization; D008213:Lymphocyte Activation; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D012513:Sarcoma, Experimental / Q000276:immunology*
D000951:Antigens, Neoplasm; D016827:CD8 Antigens; D000949:Histocompatibility Antigens Class II; D017364:Collagenases