THE CXC CHEMOKINE STROMAL CELL-DERIVED FACTOR-1 IS NOT RESPONSIBLE FOR CD8(-CELL SUPPRESSION OF SYNCYTIA-INDUCING STRAINS OF HIV-1() T)

Primary CD8(+) T cells from HIV+ asymptomatics can suppress virus prod uction from CD4(+) T cells acutely infected with either non-syncytia-i nducing (NSI) or syncytia-inducing (SI) HIV-1 isolates. NSI strains of HIV-1 predominantly use the CCR5 chemokine receptor as a fusion cofac tor, whereas fusion of T cell line-adapted SI isolates is mediated by another chemokine receptor, CXCR4. The CCR5 ligands RANTES (regulated on activation, normal T cell expressed and secreted), macrophage infla mmatory protein 1 alpha (MIP-1 alpha), and MIP-1 beta are HIV-1 suppre ssive factors secreted by CD8(+) cells that inhibit NSI viruses. Recen tly, the CXC chemokine stromal cell-derived factor 1 (SDF-1) nas ident ified as a ligand for CXCR4 and shown to inhibit SI strains. We specul ated that SDF-1 might be an effector molecule for CD8(+) suppression o f SI isolates and assessed several SDF-1 preparations for inhibition o f MV-1(LAI)-mediated cell-cell fusion, and examined levels of SDF-1 tr anscripts in CD8(+) T cells. SDF-1 fusion inhibitory activity correlat ed with the N terminus, and the alpha and beta forms of SDF-1 exhibite d equivalent fusion blocking activity. SDF-1 preparations having the N terminus described by Bleul et al. (Bleul, C.C., Fuhlbrigge, R.C., Ca sasnovas, J.M., Aiuti, A. & Springer, T.A. (1996) J. Exp. Med. 184, 11 01-1109) readily blocked HIV-1(LAI)-mediated fusion, whereas forms con taining two or three additional N-terminal amino acids lacked this act ivity despite their ability to bind and/or signal through CXCR4. Thoug h SDF-1 is constitutively expressed in most tissues, CD8 T cells conta ined extremely low levels of SDF-1 mRNA transcripts (<1 transcript/5,0 00 cells), and these levels did not correlate with virus suppressive a ctivity. We conclude that suppression of SI strains of HIV-1 by CD8(+) T cells is unlikely to involve SDF-1.