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Departments of
*
Pathology and Laboratory Medicine,
Medicine, and
Otolaryngology, University of Pennsylvania, Philadelphia, PA 19104; and
§
Institute of Viral Preparation, Russian Academy of Medicine, Moscow, Russia
Activation of T cells requires both TCR-specific ligation by direct
contact with peptide Ag-MHC complexes and coligation of the B7 family
of ligands through CD28/CTLA-4 on the T cell surface. We recently
reported that coadministration of CD86 cDNA along with DNA encoding
HIV-1 Ags i.m. dramatically increased Ag-specific CTL responses. We
investigated whether the bone marrow-derived professional APCs or
muscle cells were responsible for the enhancement of CTL responses
following CD86 coadministration. Accordingly, we analyzed CTL induction
in bone marrow chimeras. These chimeras are capable of generating
functional viral-specific CTLs against vaccinia virus and therefore
represent a useful model system to study APC/T cell function in vivo.
In vaccinated chimeras, we observed that only CD86 + Ag + MHC class I
results in 1) detectable CTLs following in vitro restimulation, 2)
detectable direct CTLs, 3) enhanced IFN-
production in an
Ag-specific manner, and 4) dramatic tissue invasion of T cells. These
results support that CD86 plays a central role in CTL induction in
vivo, enabling non-bone marrow-derived cells to prime CTLs, a property
previously associated solely with bone marrow-derived
APCs.
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