Immunomodulatory effects of a plasmid expressing B7-2 on human immunodeficiency virus-1-specific cell-mediated immunity induced by a plasmid encoding the viral antigen.
B7 co-stimulation is essential for activating resting T cells following antigen recognition by the T cell receptor. To determine whether B7 has adjuvant activities on human immunodeficiency virus type-1 (HIV-1)-specific immunity induced by inoculation of a plasmid encoding HIV-1 env and rev (DNA vaccine), B7-1 and B7-2 expression plasmids were co-inoculated with the DNA vaccine. The delayed-type hypersensitivity response and cytotoxic T lymphocyte (CTL) activity were significantly enhanced when B7-2 expression plasmid was co-inoculated with the DNA vaccine, but were unaffected when the B7-1 expression plasmid was used with the vaccine instead. The immunological response enhanced by B7-2 decreased below the level of mice immunized with the DNA vaccine in combination with CTLA4Ig, an inhibitor of the B7/CD28 co-stimulatory signal, suggesting that this signal is critical for the enhanced response induced by co-inoculation of the DNA vaccine and B7-2 expression plasmid. This enhancement appeared to occur via an interferon-gamma (IFN-gamma)-dependent mechanism, as combined administration of the B7-2 plasmid and neutralizing anti-IFN-gamma antibody abrogated the virus-specific cell-mediated immunity. These results suggest that this gene-based co-inoculation strategy using HIV-1 viral antigen and B7-2 co-stimulatory molecule could be a powerful means of combating HIV-1 infection.
Tsuji
T
T
Department of Bacteriology, Yokohama City University School of Medicine, Japan.
Hamajima
K
K
Ishii
N
N
Aoki
I
I
Fukushima
J
J
Xin
K Q
KQ
Kawamoto
S
S
Sasaki
S
S
Matsunaga
K
K
Ishigatsubo
Y
Y
Tani
K
K
Okubo
T
T
Okuda
K
K
D016915:AIDS Vaccines / Q000276:immunology*; D000069594:Abatacept; D000276:Adjuvants, Immunologic; D000818:Animals; D015703:Antigens, CD / Q000276:immunology*; D000943:Antigens, Differentiation / Q000494:pharmacology; D018122:B7-1 Antigen / Q000276:immunology; D051940:B7-2 Antigen; D060908:CTLA-4 Antigen; D003602:Cytotoxicity, Immunologic; D005260:Female; D006968:Hypersensitivity, Delayed / Q000276:immunology; D007111:Immunity, Cellular; D018796:Immunoconjugates; D007074:Immunoglobulin G / Q000096:biosynthesis; D007132:Immunoglobulin Isotypes / Q000096:biosynthesis; D007371:Interferon-gamma / Q000502:physiology; D008562:Membrane Glycoproteins / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D009132:Muscles / Q000276:immunology; D010957:Plasmids; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology
D016915:AIDS Vaccines; D000276:Adjuvants, Immunologic; D015703:Antigens, CD; D000943:Antigens, Differentiation; D018122:B7-1 Antigen; D051940:B7-2 Antigen; D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human; C497965:Cd86 protein, mouse; C556707:Ctla4 protein, mouse; D018796:Immunoconjugates; D007074:Immunoglobulin G; D007132:Immunoglobulin Isotypes; D008562:Membrane Glycoproteins; D000069594:Abatacept; D007371:Interferon-gamma