Arnold S. Rubin

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 ([ 3 H]-thymidine uptake) is dramatically suppressed, but protein synthesis ([ 3 H]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.

Characterization of the interaction of reticuloendotheliosis virus with the avian lymphoid system

Abstract Splenic lymphocytes from chickens infected with reticuloendotheliosis virus (REV) are cytostatically impaired in their ability to undergo mitogen-induced blastogenesis ([ 3 H]TdR uptake and proliferation), but are fully capable of eliciting cytotoxic reactions against allogeneic, 51 Chromium-labeled chicken erythrocytes. Spleen cells from birds with reticuloendotheliosis (RE s ) are able to suppress DNA synthesis of normal splenic lymphocytes (N s ), but are unable to inhibit 1 [ 3 H]TdR uptake by chick embryo fibroblasts. The suppression of the N s mitogenic response is not restricted by major histocompatibility (B-locus) differences between populations of RE s suppressor and N s target cells. Moreover, infection of birds with an attenuated form of REV, which replicates in the host but does not cause tumorigenesis, also leads to suppression of phytohemagglutinin-induced, [ 3 H]TdR uptake by host lymphocytes. These results are discussed in terms of the interaction between viral-infected/transformed cells and host defense mechanisms.

Generation by lipopolysaccharide of a late-acting soluble suppressor of antibody synthesis

Abstract Polyclonal stimulation of normal mouse spleen cells by lipopolysaccharide (LPS) from Salmonella typhimurium resulted in the generation of a factor which was capable of suppressing the humoral immune response in vitro . LPS effectively induced the release of the inhibitory material into the supernatants of these cultures within 24 hr. The suppressive mediator, which was similar in properties to the antigen-generated, transiently-acting soluble suppressor (TASS) reported earlier, partially abrogated (by 30–80%) the anti-sheep erythrocyte plaque-forming cell response when added to test cultures ~20 hr prior to assay for direct hemolytic plaques. Although LPS, in submitogenic doses, also was effective in depressing the in vitro hemolysin response, the inhibitory activity of residual mitogen present in the test supernatants, and that of the LPS-induced factor, were shown to be different. By use of antisera and complement treatment to selectively deplete spleen cell populations of T or B lymphocytes, it was demonstrated that B cells were essential for production of the suppressive mediator.

Dual biological function of a T-cell-derived murine immunoenhancing factor☆

Abstract Murine enhancing factor (MEF), derived from the culture fluid of mixtures of histoincompatible spleen cells, was found to have two apparently different, but perhaps closely related, biological activities. First, MEF can functionally replace T cells in nonspecifically augmenting the anti-sheep erythrocyte plaque-forming cell response of T-cell-depleted, mouse splenic B-cell cultures. Second, the mediator acts similarly to colony stimulating factor from human urine in promoting the formation of colony-forming units (CFU) in soft agar bone marrow cell cultures. This latter function of MEF was manifest in the absence of detectable increases in the level of incorporation of [ 3 H]thymidine by cultured bone marrow cells. Morphologically, the cells comprising the CFU were macrophage-like in appearance. The data suggest that MEF may function as a differentiation signal for the maturation of antigen-activated B lymphocytes into immunoglobulin-secreting cells, as well as for the modulation of hematopoietic or granulopoietic macrophage stem cells into mature, functional macrophages.

NONSPECIFIC SUPPRESSION OF THE INITIATION OF THE PRIMARY IMMUNE RESPONSE IN VITRO

Publisher Summary The chapter presents a study in which the specific stimulation of primed lymphoid cells generated the release of a factor that nonspecifically suppressed the initiation of the primary immune response against a heterologous antigen in vitro. In an attempt to determine whether the factor functioned by suppressing the inductive or productive phase of antibody synthesis, the kinetics of the appearance of anti-SRBC PFC in cultures maintained with the mediator was studied. A variety of effector molecules have been reported to mediate the function of suppressor T cells in the inhibition of B-cell humoral immune responses in vitro. Whenever T lymphocytes are triggered by antigen, suppression occurs.