B7-2 is required for the progression but not the initiation of the type 2 immune response to a gastrointestinal nematode parasite.
T cells require CD28/CTLA-4 costimulatory molecule interactions in addition to Ag-specific signals through the TCR for in vivo effector Th cell function. Some studies have suggested that the ligands for these costimulatory molecules may differentially influence effector T cell function with B7-2 favoring a type 2 response and B7-1 favoring a type 1 response, while other studies have suggested that these molecules may be redundant. The recent development of B7-2-deficient mice permits the direct analysis of the requirement of B7-2 during a type 2 immune response to an infectious pathogen. We have examined, in B7-2-deficient mice, effector Th cell function and the associated type 2 immune response following infection with Heligmosomoides polygyrus, a natural murine parasitic nematode. Elevations in cytokine gene expression and protein secretion were pronounced and comparable in inoculated B7-2-/- and B7-2+/+ mice at day 8 after H. polygyrus inoculation. However, by day 14 after infection, increases in T cell cytokine expression were markedly inhibited in H. polygyrus-inoculated B7-2-/- mice. Furthermore, elevations in serum IgE and germinal center formation were inhibited at later stages of the immune response, while elevations in serum IgG1 persisted. These findings suggest that certain T-dependent components vary in their B7-2-dependency during the type 2 immune response. They further demonstrate that B7-2 interactions are not necessary for the initiation of the type 2 immune response, but are instead required for its progression after the development of effector T cells.
Greenwald
R J
RJ
Department of Microbiology and Immunology, Uniformed Services University of the Health Sciences, Bethesda, MD 20814, USA.
Urban
J F
JF
Ekkens
M J
MJ
Chen
S
S
Nguyen
D
D
Fang
H
H
Finkelman
F D
FD
Sharpe
A H
AH
Gause
W C
WC
D000818:Animals; D015703:Antigens, CD / Q000235:genetics / Q000502:physiology*; D051940:B7-2 Antigen; D016207:Cytokines / Q000096:biosynthesis*; D004064:Digestive System / Q000276:immunology / Q000469:parasitology*; D005298:Fertility / Q000276:immunology; D018858:Germinal Center / Q000276:immunology / Q000378:metabolism / Q000469:parasitology; D008562:Membrane Glycoproteins / Q000235:genetics / Q000502:physiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D009351:Nematospiroides dubius / Q000254:growth & development / Q000276:immunology*; D017206:Strongylida Infections / Q000276:immunology / Q000469:parasitology; D018418:Th2 Cells / Q000276:immunology* / Q000378:metabolism
D015703:Antigens, CD; D051940:B7-2 Antigen; C497965:Cd86 protein, mouse; D016207:Cytokines; D008562:Membrane Glycoproteins