Effects of blocking B7-1 and B7-2 interactions during a type 2 in vivo immune response.
The costimulatory signal provided to T cells through CD28/CTLA-4 interactions is required for in vivo Th cell effector function associated with cytokine production. However, it is uncertain whether the two well-characterized ligands for these molecules, B7-1 and B7-2, differentially influence the consequent development of a type 1 or a type 2 primary response. We have examined the in vivo effects of blocking B7-1 and/or B7-2 ligand interactions on the type 2 mucosal immune response that follows oral infection of mice with the nematode parasite, Heligmosomoides polygyrus. Administration of the combination of anti-B7-1 and anti-B7-2 Abs inhibited H. polygyrus-induced increases in serum IgG1 and IgE levels, the expansion of mesenteric lymph node (MLN) germinal centers, in situ CD4+ T cell expansion, elevated blood eosinophils, and increased intestinal mucosal mast cells. Similarly, both Abs blocked MLN and Peyer's patch cytokine gene expression and elevations in MLN T cell-derived IL-4 protein secretion. However, in the same experiments, administration of either anti-B7-1 or anti-B7-2 Abs alone had little effect on any of these parameters. T cell and B cell activation was also blocked by the combination of anti-B7-2 and a B7-1-specific mutant Y100F CTLA-4Ig construct. These results suggest that to the extent that anti-B7-1 and anti-B7-2 mAbs block B7 interactions, either B7-1 or B7-2 ligand interactions can provide the required costimulatory signals that lead to T cell effector function during a type 2 in vivo immune response.
Greenwald
R J
RJ
Department of Microbiology, Uniformed Services University of the Health Sciences, Bethesda, MD 20814, USA.
Lu
P
P
Halvorson
M J
MJ
Zhou
X
X
Chen
S
S
Madden
K B
KB
Perrin
P J
PJ
Morris
S C
SC
Finkelman
F D
FD
Peach
R
R
Linsley
P S
PS
Urban
J F
JF
Gause
W C
WC
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D015703:Antigens, CD / Q000502:physiology*; D001402:B-Lymphocytes / Q000276:immunology; D018122:B7-1 Antigen / Q000502:physiology*; D051940:B7-2 Antigen; D002454:Cell Differentiation; D016207:Cytokines / Q000235:genetics; D004804:Eosinophils / Q000276:immunology; D005260:Female; D015870:Gene Expression; D018858:Germinal Center / Q000166:cytology; D018928:Immunity, Mucosal; D015847:Interleukin-4 / Q000096:biosynthesis; D008213:Lymphocyte Activation; D008407:Mast Cells / Q000276:immunology; D008562:Membrane Glycoproteins / Q000502:physiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D009351:Nematospiroides dubius / Q000276:immunology; D018418:Th2 Cells / Q000166:cytology / Q000276:immunology*
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D018122:B7-1 Antigen; D051940:B7-2 Antigen; C497965:Cd86 protein, mouse; D016207:Cytokines; D008562:Membrane Glycoproteins; D015847:Interleukin-4