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 t
hrough CD28/CTLA-4 on the T cell surface, We recently reported that coadmin
istration of CD86 cDNA along with DNA encoding HIV-1 Ags i.m. dramatically
increased Ag-specific CTL responses, We investigated whether the bone marro
w-derived professional APCs or muscle cells were responsible for the enhanc
ement of CTL responses following CD86 coadministration. Accordingly, we ana
lyzed CTL induction in bone marrow chimeras. These chimeras are capable of
generating functional viral-specific CTLs against vaccinia virus and theref
ore represent a useful model system to study APC/T cell function in vivo, I
n vaccinated chimeras, we observed that only CD86 + Ag + MHC class I result
s in 1) detectable CTLs following in vitro restimulation, 2) detectable dir
ect CTLs, 3) enhanced IFN-gamma 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 marr
ow-derived APCs.