Induction of HIV-1 replication in a chronically infected T-cell line by cytotoxic T lymphocytes.
CD8-positive cytotoxic T cells (CTLs) are activated by recognition of peptide bound to MHC class I molecules on target cells. This human leukocyte antigen-restricted process induces not only lysis of target cells but also secretion of lymphokines by the CTLs, including TNF-alpha, TNF-beta, and IFN-gamma. In this study we show that activation of HIV-1-specific CTL clones by their cognate peptide epitopes induces HIV-1 replication in the chronically HIV-1-infected T-cell line ACH-2. The HIV-1-inducing activity correlates with increased levels of TNF-alpha produced by these CTLs, and can be inhibited by anti-TNF-alpha antibodies, indicating that the effect is mediated by this cytokine. These studies suggest that activation of CTL in vivo could lead to enhanced viral replication. Although HIV-1-specific CTLs may serve as a host defense to inhibit virus replication, the induction of TNF-alpha production by these cells may facilitate viral replication in infected bystander cells, contributing to viral persistence and disease pathogenesis.
Harrer
T
T
Infectious Disease Unit, Massachusetts General Hospital, Boston 02114.
Jassoy
C
C
Harrer
E
E
Johnson
R P
RP
Walker
B D
BD
D002460:Cell Line; D002999:Clone Cells; D015497:HIV-1 / Q000502:physiology*; D006801:Humans; D008213:Lymphocyte Activation; D013601:T-Lymphocytes / Q000382:microbiology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology* / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000276:immunology / Q000502:physiology; D014779:Virus Replication
D014409:Tumor Necrosis Factor-alpha