Immune surveillance: Both CD3+ CD4+ and CD3+ CD8+ T cells control in vivo growth of P815 mastocytoma

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Abstract
The aim of this study was to examine whether a spontaneous immune response controls neoplastic growth in P815‐bearing DBA/2 mice, and to characterize the cells involved in tumor resistance in vivo. Several cell lineages such as T‐cell‐receptor (TcR)‐bearing T cells, NK cells and macrophages mediate some anti‐tumor activity in vitro. P815 was chosen as a model because it is weakly immunogenic and is a good target both for tumor‐specific, MHC‐restricted CTL‐mediated lysis and for MHC‐unrestricted lysis exerted by long‐term cultured lymphocytes or activated macrophages. Since most “NK‐like activity” in freshly isolated populations appears to be associated with CD3− cells, whereas antigen‐specific, MHC‐restricted T cells mostly express CD3 determinants, CD3 was a good marker for evaluating the role of T cells and “NK” cells in tumor resistance in vivo. The survival of anti‐CD3‐treated animals that were inoculated with tumor cells was strongly reduced (mean survival time: 17 days vs. 40 days for the control group) and was associated with increased tumor growth rate. We followed the same approach to define the T‐cell subset(s) that mediate(s) this immune response. Both CD4+ and CD8+ T cells were required for induction of immune control on neoplastic growth. The approach used has revealed the important role of CD4+ T cells in immune responses that control in vivo growth of a class‐1‐positive, class‐II‐negative tumor and suggests that these cells may play a central role in tumor resistance. Since CD4+ cells are activated by soluble, exogenous proteins, this finding may have important implications for immunotherapy.