The purpose of this project is to determine which mechanisms are the effective components of the CD8 T cell role in tumor rejection in vivo and determine how they act. The investigator will generate in vitro CTL responses to the tumor antigens of P815 using CD8 T cells from DBA/2 mice under conditions leading to T1 or T2 populations of effector T cells. He will measure the cytokine secretion, CTL activity and surface phenotype of the effector populations. In parallel cultures, he will use CD8 T cells from C57BL/6 mice to generate in vitro responses to the tumor antigens of EL-4. The effector populations will be adoptively transferred to syngeneic recipients. The effectiveness of the T1 and T2 populations will be assessed in their ability to reject already established tumors. The cell types involved in tumor rejection will be characterized. It is a central hypothesis of this study, that the cytokines liberated by the T1 and T2 populations when they encounter the tumor antigen in the host will exert a crucial influence on the nature of the host response and the likelihood of tumor rejection. The investigator will further analyze the cellular and molecular mechanisms involved in tumor rejection by generating CD8 effectors in cytokine knock out mice and by using various immunodeficient and cytokine knockout mice as recipients.
