HIV does not replicate in naive CD4 T cells stimulated with CD3/CD28.
In this report, we demonstrate that the T cell tropic strain of HIV, LAI, does not replicate in naive CD4 T cells stimulated by cross-linking CD3 and CD28. In contrast, LAI replicates well in memory CD4 T cells stimulated in the same way. Unlike this physiologically relevant stimulation, PHA stimulates productive LAI replication in both naive and memory T cells. These studies were conducted with highly purified (FACS-isolated) subsets of CD4 T cells identified by expression of both CD45RA and CD62L. Remixing of purified T cells showed that naive T cells do not suppress LAI replication in memory T cells and that memory T cells do not restore LAI expression in naive T cells. The suppression of productive LAI replication in naive T cells is not due to differential expression of viral coreceptors, nor is it due to inhibition of activation of the important HIV transcription factors, nuclear factor-kappaB and activator protein-1. The inherent resistance of naive T cells to productive HIV infection, coupled with their proliferative advantage as demonstrated here, provides a sound basis for proposed clinical therapies using ex vivo expansion and reinfusion of CD4 T cells from HIV-infected adults.
Roederer
M
M
Department of Genetics, Stanford University, California 94305-5125, USA. roederer@darwin.stanford.edu
Raju
P A
PA
Mitra
D K
DK
Herzenberg
L A
LA
Herzenberg
L A
LA
D017209:Apoptosis; D001483:Base Sequence; D018106:CD28 Antigens / Q000502:physiology*; D017252:CD3 Complex / Q000502:physiology*; D015496:CD4-Positive T-Lymphocytes / Q000821:virology*; D002455:Cell Division; D006678:HIV / Q000502:physiology*; D006801:Humans; D008969:Molecular Sequence Data; D016328:NF-kappa B / Q000378:metabolism; D013601:T-Lymphocytes / Q000378:metabolism; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D014779:Virus Replication
D018106:CD28 Antigens; D017252:CD3 Complex; D016328:NF-kappa B; D014409:Tumor Necrosis Factor-alpha; D013755:Tetradecanoylphorbol Acetate