Virus-specific cytotoxic T-lymphocytes in HIV-2-infected cynomolgus macaques.
OBJECTIVE
Specific cytotoxic T-lymphocytes (CTL) are induced in humans or monkeys after infection with HIV-1 or SIVmac, respectively. Since, like HIV-1, HIV-2 causes AIDS, our objective was to determine the characteristics of the HIV-2-specific CTL response.


METHODS
Since it is rarely possible to study cellular immunity in individuals, because of the small number of HIV-2-infected patients available in Europe and the necessity for co-operation in the performance of sequential CTL assays, cynomolgus macaques were infected with HIV-2. Autologous transformed B-lymphoblastoid cell lines infected with recombinant vaccinia viruses were used as target cells for cytotoxicity assays.


METHODS
Recombinant vaccinia viruses expressing HIV-2 genes were constructed to infect B-lymphoblastoid cell lines from macaques. These cells were used as target cells for cytotoxicity assays with peripheral blood mononuclear cells from HIV-2BEN-infected cynomolgus macaques. To characterize the effector cells, CD8+ cells were separated with immunomagnetic beads. Major histocompatibility complex (MHC) restriction of the cytotoxic cells was determined by incubation with matched or mismatched target cells.


RESULTS
HIV-2BEN-infected cynomolgus macaques raised CTL against proteins of the three major viral structural genes, gag, pol and env. The cytotoxic cells were CD8+ and their activity was MHC class I-restricted. In contrast to SIVmac-infected macaques, env-specific lysis was mediated exclusively by CD8+ cells. CTL from individual animals recognized different viral proteins and the recognition pattern varied over time.


CONCLUSIONS
Like HIV-1 and SIVmac, HIV-2 induces virus-specific CTL. The variation of antigen recognition between individual animals and over time indicates that sequential experiments are necessary to determine the complete spectrum of the CTL response of infected animals. HIV-2-infected macaques represent a suitable model for investigations into the cellular immune response against HIV.
Voss
G
G
Deutsches Primatenzentrum, Virologie und Immunologie, Göttingen, Germany.
Nick
S
S
Otteken
A
A
Lüke
W
W
Stahl-Hennig
C
C
Hunsmann
G
G
D000386:AIDS-Related Complex / Q000209:etiology; D000818:Animals; D003602:Cytotoxicity, Immunologic; D004274:DNA, Recombinant; D004195:Disease Models, Animal; D015686:Gene Products, env / Q000276:immunology; D015683:Gene Products, gag / Q000276:immunology; D015684:Gene Products, pol / Q000276:immunology; D015658:HIV Infections / Q000276:immunology*; D015498:HIV-2 / Q000235:genetics / Q000276:immunology*; D008252:Macaca fascicularis; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D013997:Time Factors; D014616:Vaccinia virus / Q000235:genetics; D014766:Viremia / Q000209:etiology
D004274:DNA, Recombinant; D015686:Gene Products, env; D015683:Gene Products, gag; D015684:Gene Products, pol