CD40-mediated stimulation contributes to lymphocyte proliferation, antibody production, eosinophilia, and mastocytosis during an in vivo type 2 response, but is not required for T cell IL-4 production.
CD40/CD40 ligand interactions are required for the development of T cell-dependent Ab responses in vivo. The role of these cell surface molecules in contributing to T cell cytokine production and the development of effector populations other than B cells and T cells is, however, less well defined. We have examined the in vivo effects of blocking CD40/CD40 ligand interactions on the type 2 mucosal immune response that follows oral inoculation of mice with the nematode parasite, Heligmosomoides polygyrus. Administration of anti-gp39 (CD40L) mAb (MR1) blocked H. polygyrus-induced elevations in serum IgG1 levels and inhibited elevations in blood eosinophils and mucosal mast cells at day 14 after inoculation. Anti-gp39 mAb markedly inhibited B cell blastogenesis 8 days after H. polygyrus inoculation but did not inhibit elevations in B cell class II MHC expression. Maximal elevations in B7-2 expression required signaling through both CD40 and the IL-4R. Elevations in T cell cytokine gene expression and elevations in the number of IL-4-secreting cells were unaffected by treatment with anti-gp39 mAb, although IL-4 production was inhibited by anti-IL-4R mAb. These results suggest that CD40/CD40L interactions are not required to activate T cells to produce cytokines but are required for the activation and proliferation of other effector cells associated with the type 2 response.
Lu
P
P
Parasite Immunobiology Laboratory, Livestock and Poultry Sciences Institute, United States Department of Agriculture, Beltsville, MD 20705, USA.
Urban
J F
JF
Zhou
X D
XD
Chen
S J
SJ
Madden
K
K
Moorman
M
M
Nguyen
H
H
Morris
S C
SC
Finkelman
F D
FD
Gause
W C
WC
D000818:Animals; D000909:Antibodies, Helminth / Q000096:biosynthesis*; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D001402:B-Lymphocytes / Q000276:immunology; D001667:Binding, Competitive / Q000276:immunology; D019013:CD40 Antigens / Q000502:physiology*; D023201:CD40 Ligand; D016207:Cytokines / Q000235:genetics; D004802:Eosinophilia / Q000097:blood / Q000276:immunology* / Q000469:parasitology; D005260:Female; D005786:Gene Expression Regulation / Q000276:immunology; D006967:Hypersensitivity / Q000276:immunology* / Q000469:parasitology; D007074:Immunoglobulin G / Q000096:biosynthesis / Q000097:blood; D015847:Interleukin-4 / Q000096:biosynthesis* / Q000276:immunology / Q000378:metabolism; D008213:Lymphocyte Activation; D008415:Mastocytosis / Q000276:immunology* / Q000469:parasitology; D008562:Membrane Glycoproteins / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D009351:Nematospiroides dubius / Q000235:genetics / Q000276:immunology; D017206:Strongylida Infections / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism*
D000909:Antibodies, Helminth; D000911:Antibodies, Monoclonal; D019013:CD40 Antigens; D016207:Cytokines; D007074:Immunoglobulin G; D008562:Membrane Glycoproteins; D023201:CD40 Ligand; D015847:Interleukin-4