In vivo migration and function of transferred HIV-1-specific cytotoxic T cells.
The persistence of HIV replication in infected individuals may reflect an inadequate host HIV-specific CD8+ cytotoxic T lymphocyte (CTL) response. The functional activity of HIV-specific CTLs and the ability of these effector cells to migrate in vivo to sites of infection was directly assessed by expanding autologous HIV-1 Gag-specific CD8+ CTL clones in vitro and adoptively transferring these CTLs to HIV-infected individuals. The transferred CTLs retained lytic function in vivo, accumulated adjacent to HIV-infected cells in lymph nodes and transiently reduced the levels of circulating productively infected CD4+ T cells. These results provide direct evidence that HIV-specific CTLs target sites of HIV replication and mediate antiviral activity, and indicate that the development of immunotherapeutic approaches to sustain a strong CTL response to HIV may be a useful adjunct to treatment of HIV infection.
Brodie
S J
SJ
Department of Laboratory Medicine, University of Washington, Seattle 98101, USA.
Lewinsohn
D A
DA
Patterson
B K
BK
Jiyamapa
D
D
Krieger
J
J
Corey
L
L
Greenberg
P D
PD
Riddell
S R
SR
D019264:Adoptive Transfer; D000595:Amino Acid Sequence; D002465:Cell Movement; D006679:HIV Seropositivity / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D008198:Lymph Nodes; D008969:Molecular Sequence Data; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology* / Q000502:physiology