RANTES, MIP-1-ALPHA AND MIP-1-BETA ARE NOT INVOLVED IN THE INHIBITIONOF HIV-1(SF33) REPLICATION MEDIATED BY CD8-CELL CLONES( T)

Objective: To determine whether CD8+ cells inhibit HIV replication in vitro through the chemokines RANTES, macrophage inflammatory protein ( MIP)-1 alpha and MIP-1 beta. Design and methods: CD8+ T-cell clones we re screened for their ability to inhibit HIV-1(SF33) replication in CD 4+ cells using p24 antigen and HIV RNA levels as end-points. It has be en suggested that such inhibition is mediated by three type cc chemoki nes: RANTES, MIP-1 alpha and MIP-1 beta. To assess whether our T-cell clones inhibited HIV replication through a similar mechanism, the clon es' ability to inhibit HIV-1(SF33) replication was compared with their secretion of RANTES, MIP-1 alpha and MIP-1 beta. Moreover, we tested the effects of neutralizing antibodies (NAb) against these factors on the anti-HIV-1(SF33) activity of our clones as well as he direct effec t of these recombinant cc-chemokines on HIV-1(SF33) replication. Resul ts: The CD8+ T-cell clones tested differed by their capacity to inhibi t HIV-1 replication. We showed no correlation between the ability of t hese clones to secrete RANTES, MIP-1 alpha and MIP-1 beta and their ab ility to repress HIV-1(SF33) replication. In addition, this inhibitory activity against HIV-1(SF33) could not be blocked by NAb directed aga inst these chemokines, nor could these chemokines significantly inhibi t HIV-1(SF33) replication in acutely infected CD4+ cells in vitro. Con clusion: The data indicate that CD8+ cells can inhibit HIV-1(SF33) rep lication in vitro by mechanisms that do not involve either cytotoxicit y or RANTES, MIP-1 alpha and MIP-1 beta.