Lymphocyte transformation for the detection of herpesvirus-induced tumor-associated antigens.

Cell-mediated immunity to fibroblasts transformed by herpes simplex virus type 2 was investigated with a lymphocyte assay system. The assay system was first standardized with phytohemagglutinin, a nonspecific stimulator of blastogenesis. Hamster splenic and blood lymphocytes reacted to phytohemagglutinin with a dose-response curve similar to that reported for other rodent species. Splenic lymphocytes from hamsters bearing isografts, induced by herpes simplex virus type 2, were transformed by cell-free virus-induced tumor antigens. The reactions with cell-free tumor antigens were dose-dependent and paralleled the findings with phytohemagglutinin. The initial transformation response of immune lymphocytes to homologous tumor antigens occurred after 72 hr incubation with antigen. Immune splenic lymphocytes from hamsters were also significantly stimulated with antigens obtained from cells productively infected with herpes simplex virus type 2. Immune lymphocytes were not stimulated with heterologous antigens from simian virus 40-transformed mouse or hamster cells. Likewise, lymphocytes from hamsters sensitized to cells transformed by simian virus 40 reacted with both simian virus 40-transformed mouse and hamster cells but did not react with cells transformed by a heterologous virus. The results suggest that under defined conditions a lymphocyte transformation assay may be useful for the specific detection of common viral-induced antigens on tumor cells.