β-Chemokines are released from HIV-1-specific cytolytic T-cell granules complexed to proteoglycans Academic Article uri icon

Overview

MeSH Major

  • Chemokine CCL5
  • Cytoplasmic Granules
  • HIV-1
  • Macrophage Inflammatory Proteins
  • Proteoglycans
  • T-Lymphocytes, Cytotoxic

abstract

  • CD8+ lymphocytes are believed to be important in host defence against the human immunodeficiency virus (HIV)-1, inhibiting HIV-1 replication through both cytolytic and non-cytolytic pathways. The cytolytic pathway involves calcium-dependent exocytosis of perforin and granzyme proteases, as well as Fas-mediated programmed cell death, whereas the noncytolytic pathway involves the release of chemokines that prevent viral entry. Using granzyme A as a marker of cytolytic granule proteins, and macrophage inflammatory protein (MIP)-1alpha and RANTES as markers of HIV-1 inhibitory chemokines, we show that these two very different mediators of viral inhibition are both localized in the cytolytic granules of HIV-1-specific CD8+ cytotoxic T lymphocytes (CTL). Following antigen-specific activation, these mediators are secreted together, facilitating both lysis of virion-producing cells and the inhibition of free virus. In addition, RANTES, MIP-1alpha and MIP-1beta are secreted by CTL as a macromolecular complex containing sulphated proteoglycans. This association appears to have a functional significance, because heparan sulphate facilitates RANTES inhibition of HIV-1 infection of monocytes.

publication date

  • February 26, 1998

Research

keywords

  • Academic Article

Identity

Language

  • eng

Digital Object Identifier (DOI)

  • 10.1038/36129

PubMed ID

  • 9495345

Additional Document Info

start page

  • 908

end page

  • 11

volume

  • 391

number

  • 6670