Immunosuppression Induced by Avian Reticuloendotheliosis Virus: Mechanism of Induction of the Suppressor Cell

Abstract

Abstract Spleen cells from chickens infected with avian reticuloendotheliosis virus (REV) become cytostatically impaired in their ability to undergo phytohemagglutinin-P (PHA)-induced blastogenesis. This inhibition of T lymphocyte proliferation is mediated by a host-derived population of suppressor cells that are activated or induced during REV infection. Oncogenic preparations of REV consist of a replication-defective transforming virus and a nontransforming, replication-competent helper virus, designated reticuloendotheliosis-associated virus (REV-A). Infection of chickens with REV-A resulted in suppression of the PHA-induced responses of spleen cells from infected birds, and a population of suppressor cells was detected in their spleens. These suppressor cells could no longer be detected 3 weeks after REV-A infection. The loss of suppressor cell activity in the spleens of REV-A infected birds was correlated temporally with the loss of detectable virus in the serum of infected birds. The immunosuppression induced by REV-A was transient since PHA-induced lymphocyte responses of infected birds returned to normal by 5 weeks after infection. Cells transformed in vitro by the replication-defective transforming virus in the absence of its helper virus, which fail to produce either infectious or uninfectious virus particles, were capable of inducing immunosuppression and reticuloendotheliosis. Cell doses of both REV-transformed, nonvirus-producing cells and REV-transformed, nonvirus-producing cells and REV-transformed virus-producing cells that were effective in inducing immunosuppression also infuced lethal reticuloendotheliosis. Antiserum directed against the major envelope glycoprotein of REV-A lysed these cells in the presence of complement, indicating that the REV-transformed, nonvirus-producing cells contain either virion glycoproteins or their precursors on the surface membranes. Chick syncytial virus, duck infectious anemia virus, and spleen necrosis virus, other nontransforming members of the reticuloendotheliosis (RE) virus group, which share cross-reactive glycoproteins with REV, also induced immunosuppression in chickens within 6 days after infection. These results suggest that the viral glycoproteins or their precursors, expressed on the membranes of RE-group virus-infected cells, may be responsible for induction of a host-derived population of suppressor cells. The possibility that other viral or host specified polypeptides may be involved in the induction or activation of the suppressor cell during avian reticuloendotheliosis cannot be ruled out. The early induction of these suppressor cells appears to play an important role in the pathogenesis of avian reticuloendotheliosis.