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

Ludwig Wagner, Otto O. Yang, Eduardo A. Garcia-Zepeda, Yimin Ge, Spyros A. Kalams, Bruce D. Walker, Mark S. Pasternack and Andrew D. Luster ()
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Eduardo A. Garcia-Zepeda: Partners AIDS Research Center and Infectious Disease Units, Massachusetts General Hospital and Harvard Medical School
Yimin Ge: Partners AIDS Research Center and Infectious Disease Units, Massachusetts General Hospital and Harvard Medical School
Spyros A. Kalams: Partners AIDS Research Center and Infectious Disease Units, Massachusetts General Hospital and Harvard Medical School
Bruce D. Walker: Partners AIDS Research Center and Infectious Disease Units, Massachusetts General Hospital and Harvard Medical School
Mark S. Pasternack: Partners AIDS Research Center and Infectious Disease Units, Massachusetts General Hospital and Harvard Medical School
Andrew D. Luster: Partners AIDS Research Center and Infectious Disease Units, Massachusetts General Hospital and Harvard Medical School

Nature, 1998, vol. 391, issue 6670, 908-911

Abstract: 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 pathways1,2,3. The cytolytic pathway involves calcium-dependent exocytosis of perforin and granzyme proteases, as well as Fas-mediated programmed cell death4, whereas the noncytolytic pathway involves the release of chemokines that prevent viral entry5. 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.

Date: 1998
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DOI: 10.1038/36129

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