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Metabolism Branch, Division of Clinical Sciences, National Cancer Institute, Bethesda, MD 20892
IL-15 is a T cell growth factor that shares many biological
activities with IL-2 and uses the same ß/
polypeptides of the
IL-2R complex for signal transduction. Accumulating evidence implicates
an important role for this cytokine in the inflammatory response of the
host. Consistent with such a role, IL-15 has been shown to be a
chemoattractant for T lymphocytes, NK cells, and neutrophils. Extending
these observations, we now show that IL-15 is a potent inducer of CC-,
CXC-, and C-type chemokines in T lymphocytes. In addition, we
demonstrate that IL-15 induces CC chemokine receptors, but not CXC
chemokine receptors, in a dose-dependent manner. Thus, our findings
suggest that the proinflammatory effects of IL-15 at least in part may
be due to the induction of chemokines and their receptors in T cells.
Furthermore, we demonstrate that IL-15 promotes entry and replication
of macrophage-tropic HIV in T lymphocytes and suggest a plausible
mechanism by which IL-15, a cytokine that is elevated in HIV-infected
individuals, may promote the transition of HIV displaying the M-tropic
phenotype primarily associated with the initial transmission into the T
cell-tropic phenotype that predominates as the disease
progresses.
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