Contact-mediated suppression of mitogen-induced responsiveness by spleen cells in reticuloendotheliosis virus-induced tumorigenesis.

Spleen cells from chickens inoculated with reticuloendotheliosis virus (REV), a C-type RNA tumor virus, are suppressed in their ability to respond to the mitogens phytohemagglutinin-P (PHA) and lipopolysaccharide (LPS). DNA synthesis ([³H]-thymidine uptake) is dramatically suppressed, but protein synthesis ([³H]leucine uptake) and trypan blue dye exclusion are only moderately decreased or unaffected, indicating that viability is not substantially reduced. Normal spleen cells (N_s) prestimulated with mitogen become similarly suppressed when mixed at a ratio of 1: 1 with spleen cells from birds with reticuloendotheliosis (RE_s). Removal of adherent cells does not abrogate the suppressive effects. No suppressor substance can be isolated from the supernatant fluids of cultured RE_s. Moreover, no suppression occurs across 0.4-μm Nuclepore filters in 2-ml double-diffusion chambers. The REV-induced suppression can be transferred to normal cells with the 8000g supernatants and pellets of lysed RE_s which contain little or no detectable REV by reverse transcriptase assay, indicating that the suppressive agent is not intact REV. Similar preparations from an REV-transformed cell line do not suppress N_s, Centrifugation at 73,500g removes suppressing activity from the lysed RE_s, preparations. These results support the hypothesis that the suppression in REV-induced tumorigenesis is contact-mediated.