Effect of human immunodeficiency virus type-1 envelope glycoprotein gp160
on cytokine production from cord-blood T cells
S Than, N Oyaizu, RN Pahwa, VS Kalyanaraman and S Pahwa
Department of Pediatrics, North Shore University Hospital-Cornell
University Medical College, Manhasset, NY 11030.
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.
Volume 84,
Issue 1,
pp. 184-188,
07/01/1994
Copyright © 1994 by The American Society of Hematology