H-2 antigen expression on teratocarcinoma cells passaged in genetically resistant mice is regulated by lymphoid cells.

Previous studies have demonstrated that resistance and susceptibility to the 402AX testicular teratocarcinoma are under genetic control in the mouse. Under normal culture conditions or when passaged in genetically susceptible hosts, the nullipotent 402AX cells do not express H-2 antigens. However, when passaged in genetically resistant animals, the tumor cells become strongly positive for H-2 antigens in the absence of other indications of differentiation. These studies suggested that H-2 antigen modulation on teratocarcinoma cells is mandatory for an effective host cell-mediated immune response against this tumor. The present studies further examine the role of H-2 antigen modulation on teratocarcinoma cells and determine which host cell populations are mediating H-2 modulation on the tumor cells. Reconstitution of lethally irradiated susceptible hosts with resistant bone marrow extends the mean survival time of the host but does not confer complete resistance. Teratocarcinoma cells passaged in such reconstituted hosts do not express H-2 antigens. Two lines of evidence suggest that H-2 antigen modulation is mediated by lymphoid cells: (i) sublethal irradiation of genetically resistant hosts inhibits H-2 antigen modulation on teratocarcinoma cells passaged in vivo and (ii) immunological priming can overcome the loss of H-2 modulation that is normally associated with aging in genetically resistant hosts. Genetically susceptible mice can be fully reconstituted for tumor rejection and H-2 antigen expression on teratocarcinoma cells by reconstitution with genetically resistant bone marrow plus lymphoid cells from tumor-primed resistant hosts. These results: (i) imply the necessity for H-2 antigens on tumor cells for an effective host cell-mediated immune response against the tumor, and (ii) indicate that host lymphoid cells regulate H-2 antigen expression on tumor cells passaged in vivo.