Interactions between autologous CD4+ and CD8+ T lymphocytes and human squamous cell carcinoma of the head and neck

The autotumor (AuTu)-specific cytolytic T lymphocyte (CTL) line established from the peripheral blood of a patient with oral squamous cell carcinoma (Cancer Res. 53, 1461, 1993) contained >95% of CD8+ and <5% of CD4+ T cells. This CTL line was infected with Herpesvirus saimiri to increase its life span in culture. Two transformed T cell sublines were obtained: the monoclonal CD4+ line (TCR Vbeta2+ V alpha15+) and the oligoclonal CD8+ line (TCR Vbeta6+, Vbeta7+ and Vbeta9+) both of which were maintained in culture for >6 months without AuTu restimulation and which did not produce any virus. The virus-transformed and untransformed T cell lines were compared for phenotypic and functional characteristics, including the ability to kill AuTu, induce expression of the major histocompatibility complex (MHC) antigens on AuTu, and respond to AuTu by cytokine production and/or proliferation. The H. saimiri-transformed CD4+ T cells expressed higher levels of surface adhesion molecules and CD45RO than untransformed cells and lysed AuTu by inducing DNA fragmentation as well as necrosis. This lysis was inhibited by antibodies to CD4 but not to class I or II MHC molecules. The CD4+ T cells produced IL2, TNF-alpha, and GM-CSF and proliferated in response to AuTu. They induced and sustained proliferation of CD8+ T cells in cocultures with AuTu. Supernatants obtained from cocultures of the CD4+ T cells with AuTu also induced proliferation of the CD8+ T cell line. In contrast, the H. saimiri-transformed CD8+ T cells did not kill AuTu or release cytokines in response to AuTu. However, upon pretreatment of AuTu with IFN-gamma to increase expression of MHC antigens, these T cells regained the ability to recognize and kill AuTu targets. Coincubation of AuTu with the CD4+ or CD8+ T cells significantly augmented expression of class I and II MHC antigens on AuTu. These data indicate that H. saimiri-transformed tumor-reactive T cell lines provide a useful model of interactions between immune effector cells and AuTu, and that CD4+ T cells play a critical role in the regulation of immune responses to squamous cell carcinoma of the head and neck.