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

Abstract

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 8000 g 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 73,500 g removes suppressing activity from the lysed RE s, preparations. These results support the hypothesis that the suppression in REV-induced tumorigenesis is contact-mediated.