B7-1 and B7-2 monoclonal antibodies modulate the severity of murine Lyme arthritis.
We assessed the role of B7-1 and B7-2 costimulatory molecules on the course of murine Lyme borreliosis because experimental Lyme arthritis is dependent, at least partially, upon the development of the host immune response and these costimulatory molecules have been implicated in CD4+ T-cell differentiation. We demonstrated that Borrelia burgdorferi infection upregulated the surface expression of B7-1 and B7-2 in macrophages and B7-2 expression in B cells. Anti-B7-2 monoclonal antibody (MAb) or both anti-B7-2 and anti-B7-1 MAbs produced a dose-dependent increase in the severity of Lyme arthritis in C3H/HeN mice. In contrast, the administration of an anti-B7-1 MAb reduced the degree of arthritis. These effects occurred independently of significant alteration in B. burgdorferi-specific immune responses, including splenocyte proliferative responses to B. burgdorferi, B. burgdorferi antibody levels and specificity, and mRNA levels of gamma interferon, interleukin-4 (IL-4), IL-10, and IL-12 in the spleen. These results demonstrate that signaling delivered by B7-1 and B7-2 plays a role in determining the severity of acute murine Lyme arthritis.
Anguita
J
J
Department of Internal Medicine, Yale University School of Medicine, New Haven, Connecticut 06520-8031, USA.
Roth
R
R
Samanta
S
S
Gee
R J
RJ
Barthold
S W
SW
Mamula
M
M
Fikrig
E
E
D000818:Animals; D000907:Antibodies, Bacterial / Q000097:blood; D000911:Antibodies, Monoclonal / Q000276:immunology*; D015703:Antigens, CD / Q000502:physiology*; D001170:Arthritis, Infectious / Q000209:etiology* / Q000628:therapy; D018122:B7-1 Antigen / Q000502:physiology*; D051940:B7-2 Antigen; D007371:Interferon-gamma / Q000097:blood; D008193:Lyme Disease / Q000209:etiology* / Q000628:therapy; D008562:Membrane Glycoproteins / Q000502:physiology*; D051379:Mice; D008809:Mice, Inbred C3H
D000907:Antibodies, Bacterial; D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D018122:B7-1 Antigen; D051940:B7-2 Antigen; C497965:Cd86 protein, mouse; D008562:Membrane Glycoproteins; D007371:Interferon-gamma