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

L. Wagner, O. O. Yang, E. A. Garcia-Zepeda, Yimin Ge, S. A. Kalams, B. D. Walker, M. S. Pasternack, A. D. Luster

Research output: Contribution to journalArticle

296 Scopus citations

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)-1α 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-1α and MIP-1β 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.

Original languageEnglish (US)
Pages (from-to)908-911
Number of pages4
JournalNature
Volume391
Issue number6670
DOIs
StatePublished - Feb 26 1998

ASJC Scopus subject areas

  • General

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