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

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-I-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.

Cyclophosphamide treatment induces rejection of established P815 mastocytoma by enhancing CD4 priming and intratumoral infiltration of P1E/H‐2Kd‐specific CD8+ T cells

“…b ). The increased tumor growth in mice treated with anti‐CD4 or anti‐CD8 mAb only was consistent with our previous observation that CD4 + and CD8 + T lymphocytes control the in vivo growth of P815 …”

Dendritic cells fused with mastocytoma cells elicit therapeutic antitumor immunity

“…Experiments are under way to identify the antigens that are the targets of the immune response induced by hybrid cells in vivo. Whether P815-encoded peptide(s) possess class II binding ability is presently unknown but is suggested by the involvement of class II-restricted CD4 ϩ cells in in vivo resistance (Flamand et al, 1990) and the induction of DTH to P815AB antigen (Bianchi et al, 1996). Class II-restricted epitopes have been demonstrated in P815AB by functional assays and by generating CD4 ϩ specific clones (Grohmann et al, 1997).…”

Tumorigenicity of mouse T lymphoma cells is controlled by the level of major histocompatibility complex class I H-2Kk antigens

“…We therefore selectively eliminated CD8 + immune effector cells by successive injections of anti-CD8b Mabs, according to a protocol that had proven successful for other tumors [20]. We effectively eliminated CD8 + T-cell function, since the number of CD8 + T-cells was significantly decreased (number of fluorescent cells fell from 5% to less than 1.5%).…”

“…Depletion experiments with anti-CDS/3 ascites (H35.7.2) [19] purified on a protein A-sepharose column, were performed by injecting 1 mg/ml intraperitoneally (i.p.) on the same day as the injection of the BW cells and 0.25 mg i.p., 7 days later [20]. The H35.7.2 hybridoma and ascites were generously provided by Dr M. Moser (Universite Libre de Bruxelles, Belgium).…”