CD8+ cells from HIV-2-infected baboons control HIV replication.
OBJECTIVE
To analyze the CD8+ cell antiviral immune response in HIV-2-infected baboons.


METHODS
Baboons were infected with clinical isolates of HIV-2, CD8+ cells were isolated from phytohemagglutinin (PHA)-stimulated baboon peripheral blood mononuclear cells (PBMC). These cells were cultured with PHA-stimulated CD4+ cells acutely infected with HIV-2 at several CD8+:CD4+ cell ratios. Control of HIV-2 replication was determined by comparing peak levels of HIV-2 replication in fluids from CD8+:CD4+ cell cocultures with those in fluids from infected CD4+ cells cultured alone.


RESULTS
CD8+ cells from HIV-2-infected baboons inhibited HIV-2 replication in acutely infected autologous CD4+ cells to a significantly greater extent than did CD8+ cells from uninfected baboons (P = 0.0001). At the beginning of the acute phase of HIV-2 infection, CD8+ cells showed either a transient reduction or loss in the antiviral activity. In some cases the CD8+ cell response enhanced HIV-2 replication. Subsequently, the strength of the CD8+ cell antiviral activity increased concomitant with a decrease in the HIV-2 load in the PBMC. Suppression of HIV replication could be demonstrated with filtered fluid from CD8+ cells. Other studies indicated that infected CD4+ cells are lost during coculture of CD8+ cells with infected CD4+ cells.


CONCLUSIONS
CD8+ cells of HIV-2-infected baboons develop substantial anti-HIV-2 activity following HIV-2 infection, which may account in part for the low frequency of pathogenesis in HIV-2-infected baboons. Studies to elucidate the mechanism of this CD8+ cell antiviral activity suggest that it is mediated in part by a soluble antiviral factor, but primarily in association with the loss of infected CD4+ cells.
Blackbourn
D J
DJ
Department of Medicine, University of California, San Francisco 94143, USA.
Locher
C P
CP
Ramachandran
B
B
Barnett
S W
SW
Murthy
K K
KK
Carey
K D
KD
Brasky
K M
KM
Levy
J A
JA
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology / Q000821:virology; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000821:virology; D002478:Cells, Cultured; D018920:Coculture Techniques; D015658:HIV Infections / Q000097:blood / Q000821:virology; D015498:HIV-2 / Q000276:immunology* / Q000502:physiology; D006801:Humans; D008221:Lymphoid Tissue / Q000166:cytology; D010215:Papio; D014779:Virus Replication