CD86 (B7-2) can function to drive MHC-restricted antigen-specific CTL responses in vivo.
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-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 marrow-derived APCs.
Agadjanyan
M G
MG
Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia 19104, USA. agadjany@mail.med.upenn.edu
Kim
J J
JJ
Trivedi
N
N
Wilson
D M
DM
Monzavi-Karbassi
B
B
Morrison
L D
LD
Nottingham
L K
LK
Dentchev
T
T
Tsai
A
A
Dang
K
K
Chalian
A A
AA
Maldonado
M A
MA
Williams
W V
WV
Weiner
D B
DB
D000818:Animals; D015703:Antigens, CD / Q000008:administration & dosage* / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D018122:B7-1 Antigen / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology; D051940:B7-2 Antigen; D002465:Cell Movement / Q000276:immunology; D003602:Cytotoxicity, Immunologic / Q000187:drug effects / Q000235:genetics; D018984:Epitopes, T-Lymphocyte / Q000276:immunology*; D005260:Female; D006183:H-2 Antigens / Q000235:genetics / Q000276:immunology* / Q000494:pharmacology; D019302:HIV Envelope Protein gp160 / Q000096:biosynthesis / Q000235:genetics; D064532:Histocompatibility Antigen H-2D; D008213:Lymphocyte Activation / Q000187:drug effects / Q000235:genetics; D008562:Membrane Glycoproteins / Q000008:administration & dosage* / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018482:Muscle, Skeletal / Q000276:immunology / Q000378:metabolism / Q000821:virology; D015202:Protein Engineering; D011828:Radiation Chimera; D013234:Stem Cells / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014162:Transfection / Q000276:immunology; D001613:beta 2-Microglobulin / Q000235:genetics
D015703:Antigens, CD; D018122:B7-1 Antigen; D051940:B7-2 Antigen; C497965:Cd86 protein, mouse; D018984:Epitopes, T-Lymphocyte; D006183:H-2 Antigens; D019302:HIV Envelope Protein gp160; D064532:Histocompatibility Antigen H-2D; D008562:Membrane Glycoproteins; D001613:beta 2-Microglobulin