The immune response induced in vivo by dendritic cells is dependent on B7-1 or B7-2, but the inhibition of both signals does not lead to tolerance.
Dendritic cells (DC) can be used as physiological adjuvant in vivo. Indeed, a single injection of DC, pulsed in vitro with antigen, induces activation of specific T and B lymphocytes in syngeneic mice. The unique capacity of DC to sensitize naive T lymphocytes correlates with elevated expression of MHC antigens as well as co-stimulatory molecules. The aim of this work was to evaluate the functional role of the individual CD28 ligands in the induction of primary humoral and cellular responses, and to characterize the nature of the immune response induced in the presence of selected co-stimulatory molecules. Our data show that the primary response is strictly B7 dependent, and that B7-1 and B7-2 mediate overlapping co-stimulatory functions, as either molecule alone is sufficient to initiate an immune reaction. Inhibition of B7-1 and B7-2, however, does not lead to tolerance as predicted by the two-signal hypothesis. Rather, recognition of antigen in the absence of B7 appears as a null event, since subsequent immunogenic stimulation results in a primary response. Blockade of B7-2 co-stimulatory molecules significantly inhibits antigen-specific IgG1 but not IgG2a production, suggesting that B7-2 may direct the development of Th2 cells. These data emphasize the critical role of the CD28/B7 pathway in the induction of the immune response by DC, which appear to be the initiating antigen-presenting cells in situ.
Lespagnard
L
L
Département de Biologie Moléculaire, Université Libre de Bruxelles, Rhode-Saint-Genèse, Belgium.
Mettens
P
P
De Smedt
T
T
Bazin
H
H
Urbain
J
J
Leo
O
O
Moser
M
M
D000069594:Abatacept; D000293:Adolescent; D000818:Animals; D015703:Antigens, CD / Q000502:physiology*; D000943:Antigens, Differentiation / Q000502:physiology; D018122:B7-1 Antigen / Q000502:physiology*; D051940:B7-2 Antigen; D018106:CD28 Antigens / Q000502:physiology; D060908:CTLA-4 Antigen; D003713:Dendritic Cells / Q000502:physiology*; D005260:Female; D006801:Humans; D007108:Immune Tolerance; D018796:Immunoconjugates; D007074:Immunoglobulin G / Q000096:biosynthesis / Q000145:classification; D008562:Membrane Glycoproteins / Q000502:physiology*; D051379:Mice; D008811:Mice, Inbred DBA; D013601:T-Lymphocytes / Q000276:immunology
D015703:Antigens, CD; D000943:Antigens, Differentiation; D018122:B7-1 Antigen; D051940:B7-2 Antigen; D018106:CD28 Antigens; C497964:CD86 protein, human; D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human; C497965:Cd86 protein, mouse; C556707:Ctla4 protein, mouse; D018796:Immunoconjugates; D007074:Immunoglobulin G; D008562:Membrane Glycoproteins; D000069594:Abatacept