Document 0182 DOCN M9480182 TI Effect of human immunodeficiency virus type-1 envelope glycoprotein gp160 on cytokine production from cord-blood T cells. DT 9410 AU Than S; Oyaizu N; Pahwa RN; Kalyanaraman VS; Pahwa S; Department of Pediatrics, North Shore University Hospital-Cornell; University Medical College, Manhasset, NY 11030. SO Blood. 1994 Jul 1;84(1):184-8. Unique Identifier : AIDSLINE MED/94289699 AB We have recently demonstrated that the human immunodeficiency virus type 1 (HIV-1) envelope glycoprotein gp160 enhances the in vitro differentiation of hematopoietic myeloid progenitor cells derived from cord blood by inducing secretion of colony-stimulating factor(s) (CSF) in T cells, presumably through the interaction of gp160 with CD4 molecules. In this study, we investigated the gp 160-induced humoral CSFs in cord blood by enzyme-linked immunosorbent assay (ELISA) and by polymerase chain reaction on reverse-transcribed mRNA (RT-PCR). We demonstrate that gp160 can induce interleukin (IL)-3, IL-6, and granulocyte-macrophage CSF (GM-CSF) protein secretion only in purified cord-blood T cells (CB-T) and not in detectable amounts in whole cord blood cells (WCB); cytokine mRNA induction occurred in purified CB-T and WCB, but was significantly greater in the former. Treatment of gp160 with soluble CD4 (sCD4) abolished the secretion of all three cytokines in CB-T cells, which suggests that interaction of gp160 with CD4 molecules is required for the secretion of these cytokines from CB-T cells. However, in WCB cells, sCD4 treatment of gp160 resulted in inhibition of only IL-3 and GM-CSF mRNA, whereas IL-6 secretion was enhanced. Purified cord-blood monocytes secreted only IL-6 in response to gp160, and the gp160-induced IL-6 secretion by monocytes was also further increased by gp160 + sCD4 complex. Furthermore, monocyte culture supernatants suppressed gp160-induced IL-3 secretion from CB-T cells. These findings indicate that (1) CB-T cells are a potent source of gp160-induced hematopoietic cytokines, and (2) that different mechanisms are involved in the induction of IL-6 by gp160 in the T- and non-T-cell fractions of cord blood. The ability of HIV gp160 to induce hematopoietic CSFs in cord blood may be important in HIV pathogenesis. DE Antigens, CD4/PHYSIOLOGY Antigens, CD45/ANALYSIS Base Sequence Cytokines/*BIOSYNTHESIS Fetal Blood/*METABOLISM Gene Products, env/*PHARMACOLOGY Granulocyte-Macrophage Colony-Stimulating Factor/BIOSYNTHESIS/ GENETICS Human *HIV-1 Infant, Newborn Interleukin-3/BIOSYNTHESIS/GENETICS Interleukin-6/BIOSYNTHESIS/GENETICS Molecular Sequence Data Protein Precursors/*PHARMACOLOGY RNA, Messenger/ANALYSIS Support, U.S. Gov't, P.H.S. T-Lymphocytes/*METABOLISM JOURNAL ARTICLE SOURCE: National Library of Medicine. NOTICE: This material may be protected by Copyright Law (Title 17, U.S.Code).