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.