Analysis of lymphoid cells responding to virus- and tumor- associated antigens in spleens of syngeneic mouse mammary tumor systems with low and high oncogenic potentials

Nylon-nonadherent cells obtained from the spleens of tumor bearers of two BALB/c mouse colonies with different oncogenic potentials were found to be the lymphocyte subclass responsive in blastogenesis to their tumor-associated antigens (TAA). Thus Thy 1-positive spleen cells from BALB/cCrgl mice that received implants of a syngeneic, chemically induced mammary tumor and BALB/cfC3H mice bearing spontaneous mammary tumors (SMT) incorporated high levels of [³H]thymidine after in vitro exposure to homologous TAA preparations. These responses were evident in animals at the early stages of tumorigenesis but could not be detected in the T-cells of animals with large tumor burdens. Responses to murine mammary tumor virus (MuMTV) antigens were observed likewise in the nylon-nonadherent spleen cell population of the MuMTV-positive BALB/cfC3H mice bearing small SMT. The responsiveness to viral antigens also decreased with progression of the disease. In BALB/cCrgl mice, which have a low incidence of SMT and are devoid of intact mouse mammary tumor virions, T-lymphocytes appeared to be nonresponsive to MuMTV antigens, but nylon-adherent spleen lymphocytes were capable of being stimulated by MuMTV. The blastogenic response of these B-lymphocytes was not altered by tumor initiation or progression. Depletion studies with the use of either anti-Thy 1 or antisurface immunoglobulin sera plus complement confirmed the validity of the results observed in the nylon wool column separation studies. Flow cytometric analyses of the spleen cells of tumor-bearing mice from both colonies revealed a depression of the levels of T-lymphocytes with increasing tumor burden while there was no decrease in the percentage of B-cells. These results provided a possible explanation for the loss of blastogenic response to tumor antigens and to MuMTV observed in spleen cells of BALB/cfC3H mice with increasing tumor burden and for the unalterable responses to MuMTV that appeared in splenocytes of BALB/cCrgl mice at all stages of tumorigenesis.