Effect of human immunodeficiency virus type-1 envelope glycoprotein gp160 on cytokine production from cord-blood T cells.
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.
Department of Pediatrics, North Shore University Hospital-Cornell University Medical College, Manhasset, NY 11030.
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S
Than
N
N
Oyaizu
R N
RN
Pahwa
V S
VS
Kalyanaraman
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S
Pahwa
D001483:Base Sequence; D015704:CD4 Antigens / Q000502:physiology; D016207:Cytokines / Q000096:biosynthesis*; D005312:Fetal Blood / Q000378:metabolism*; D015686:Gene Products, env / Q000494:pharmacology*; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000096:biosynthesis / Q000235:genetics; D019302:HIV Envelope Protein gp160; D015497:HIV-1; D006801:Humans; D007231:Infant, Newborn; D007377:Interleukin-3 / Q000096:biosynthesis / Q000235:genetics; D015850:Interleukin-6 / Q000096:biosynthesis / Q000235:genetics; D017493:Leukocyte Common Antigens / Q000032:analysis; D008969:Molecular Sequence Data; D011498:Protein Precursors / Q000494:pharmacology*; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1; D012333:RNA, Messenger / Q000032:analysis; D013601:T-Lymphocytes / Q000378:metabolism*
D015704:CD4 Antigens; D016207:Cytokines; D015686:Gene Products, env; D019302:HIV Envelope Protein gp160; D007377:Interleukin-3; D015850:Interleukin-6; D011498:Protein Precursors; D012333:RNA, Messenger; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D017493:Leukocyte Common Antigens; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1