RANTES, MIP-1 alpha and MIP-1 beta are not involved in the inhibition of HIV-1SF33 replication mediated by CD8+ T-cell clones.
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.


METHODS
CD8+ T-cell clones were screened for their ability to inhibit HIV-1SF33 replication in CD4+ cells using p24 antigen and HIV RNA levels as endpoints. It has been suggested that such inhibition is mediated by three type cc chemokines: RANTES, MIP-1 alpha and MIP-1 beta. To assess whether our T-cell clones inhibited HIV replication through a similar mechanism, the clones' ability to inhibit HIV-1SF33 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-1SF33 activity of our clones as well as the direct effect of these recombinant cc-chemokines on HIV-1SF33 replication.


RESULTS
The CD8+ T-cell clone; tested differed by their capacity to inhibit HIV-1 replication. We showed no correlation between the ability of these clones to secrete RANTES, MIP-1 alpha and MIP-1 beta and their ability to repress HIV-1SF33 replication. In addition, this inhibitory activity against HIV-1SF33 could not be blocked by NAb directed against these chemokines, nor could these chemokines significantly inhibit HIV-1SF33 replication in acutely infected CD4+ cells in vitro.


CONCLUSIONS
The data indicate that CD8+ cells can inhibit HIV-1SF33 replication in vitro by mechanisms that do not involve either cytotoxicity or RANTES, MIP-1 alpha and MIP-1 beta.
Paliard
X
X
Chiron Corporation, Virology and Vaccine Development, Emeryville, CA 94608, USA.
Lee
A Y
AY
Walker
C M
CM
D000906:Antibodies / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000378:metabolism*; D054407:Chemokine CCL4; D018946:Chemokine CCL5 / Q000378:metabolism*; D002999:Clone Cells; D016655:HIV Core Protein p24 / Q000378:metabolism; D015497:HIV-1 / Q000502:physiology*; D006801:Humans; D019402:Macrophage Inflammatory Proteins / Q000378:metabolism*; D014779:Virus Replication
D000906:Antibodies; D054407:Chemokine CCL4; D018946:Chemokine CCL5; D016655:HIV Core Protein p24; D019402:Macrophage Inflammatory Proteins