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dc.contributor.authorMalick, Adrien Paulen
dc.description.abstractA heat-stable soluble inhibitor of T cell proliferation was demonstrated in splenic and peritoneal macrophage (Mφ) culture supernatants. Concentrated supernatants were prostaglandin E₂ (PGE₂)-free and yet inhibited proliferation in the mixed lymphocyte reaction (MLR) and mitogen assays. The high mw inhibitory factor was apparently >67 kd, as shown by S-200 Sephacryl chromatography and gel electrophoresis. DEAE-Cellulose chromatography suggested that the pl of the inhibitory factor was < 7.7. lsoelectric focusing revealed that the Mφ-mediated inhibitory activity differed in charge, with a pl of 6.5-7.6 for normal hosts and 4.0-6.0 for tumor bearing hosts (TBH). Normal and TBH Mφ supernatants showed different hydroxylapatite fractionation, with the latter being resistant to proteolytic enzymes but sensitive to neuraminidase. Lectins such as wheat germ agglutinin, concanavalin A, Ricin communi: and Bandeirea simplicifolia were not useful in affinity purification of the high mw inhibitory monokine. Sugar-BSA conjugates suggested that inhibitory activity was vested in a terminal ßl,4 linked galactose. The inhibitory activity was apparently hydrophobic and heat·stable, but heat-stability was lost if supernatants were boiled at an acidic pH. The high mw monokine inhibited the proliferation of P388D₁ and A4A cells, but enhanced the proliferation of BW 5147.3 cells. Time course addition to the MLR revealed that PGE; may be required for inhibitory activity to be manifested early (0 and 24 hr) but not if the high molecular weight (mw) inhibitor was added late (>48 hr). Indomethacin blocked activity of the inhibitory factor early in the MLR using normal host T cells and augmented the proliferation of TBH T cells in the MLR. Both normal and TBH Mo supernatants suppressed the generation of interleukin 2 but with a dose- and time·dependent difference. Cell cycle analysis of mitogen- stimulated cells revealed that TBH M

dc.format.extentxv, 148 leavesen
dc.publisherVirginia Polytechnic Institute and State Universityen
dc.relation.isformatofOCLC# 16988671en
dc.rightsIn Copyrighten
dc.subjectT cellsen
dc.subject.lccLD5655.V856 1987.M343en
dc.subject.lcshT cellsen
dc.titleTumor-induced immunosuppression: Contribution of a high molecular weight inhibitor and Prostaglandin E2en
dc.description.degreePh. D.en D.en Polytechnic Institute and State Universityen

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