INTERACTIONS BETWEEN AUTOLOGOUS CD4(-LYMPHOCYTES AND HUMAN SQUAMOUS-CELL CARCINOMA OF THE HEAD AND NECK() AND CD8(+) T)

The autotumor (AuTu)-specific cytolytic T lymphocyte (CTL) line establ ished from the peripheral blood of a patient with oral squamous cell c arcinoma (Cancer Res. 53, 1461, 1993) contained >95% of CD8(+) and <5% of CD4(+) T cells. This CTL line was infected with Herpesvirus saimir i to increase its life span in culture. Two transformed T cell subline s were obtained: the monoclonal CD4(+) line (TCR V beta 2(+)V alpha 15 (+)) and the oligoclonal CD8(+) line (TCR V beta 6(+), V beta 7(+) and V beta 9(+)) both of which were maintained in culture for > 6 months without AuTu restimulation and which did not produce any virus. The vi rus-transformed and untransformed T cell lines were compared for pheno typic and functional characteristics, including the ability to kill Au Tu, induce expression of the major histocompatibility complex (MHC) an tigens on AuTu, and respond to AuTu by cytokine production and/or prol iferation. The H. saimiri-transformed CD4(+) T cells expressed higher levels of surface adhesion molecules and CD45RO than untransformed cel ls and lysed AuTu by inducing DNA fragmentation as well as necrosis. T his 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 proli feration of CD8(+) T cells in cocultures with AuTu, Supernatants obtai ned from cocultures of the CD4(+) T cells with AuTu also induced proli feration of the CD8(+) T cell line. In contrast, the H. saimiri-transf ormed CD8(+) T cells did not kill AuTu or release cytokines in respons e to AuTu. However, upon pretreatment of AuTu with IFN-gamma to increa se expression of MHC antigens, these T cells regained the ability to r ecognize and kill AuTu targets. Coincubation of AuTu with the CD4(+) o r 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 bet ween immune effector cells and AuTu, and that CD4(+) T cells play a cr itical role in the regulation of immune responses to squamous cell car cinoma of the head and neck. (C) 1997 Academic Press.