TY - JOUR
T1 - β-Chemokines are released from HIV-1-specific cytolytic T-cell granules complexed to proteoglycans
AU - Wagner, L.
AU - Yang, O. O.
AU - Garcia-Zepeda, E. A.
AU - Ge, Yimin
AU - Kalams, S. A.
AU - Walker, B. D.
AU - Pasternack, M. S.
AU - Luster, A. D.
PY - 1998/2/26
Y1 - 1998/2/26
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=0032567942&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0032567942&partnerID=8YFLogxK
U2 - 10.1038/36129
DO - 10.1038/36129
M3 - Article
C2 - 9495345
AN - SCOPUS:0032567942
SN - 0028-0836
VL - 391
SP - 908
EP - 911
JO - Nature
JF - Nature
IS - 6670
ER -