The role of OX40 ligand interactions in the development of the Th2 response to the gastrointestinal nematode parasite Heligmosomoides polygyrus.
In these studies, we examined the effects of OX40 ligand (OX40L) deficiency on the development of Th2 cells during the Th2 immune response to the intestinal nematode parasite Heligmosomoides polygyrus. Elevations in IL-4 production and total and Ag-specific serum IgE levels were partially inhibited during both the primary and memory immune responses to H. polygyrus in OX40L(-/-) mice. The host-protective memory response was compromised in OX40L(-/-) mice, as decreased worm expulsion and increased egg production were observed compared with H. polygyrus-inoculated OX40L(+/+) mice. To further examine the nature of the IL-4 defect during priming, adoptively transferred DO11.10 T cells were analyzed in the context of the H. polygyrus response. Although Ag-specific T cell IL-4 production was reduced in the OX40L(-/-) mice following immunization with OVA peptide plus H. polygyrus, Ag-specific T cell expansion, cell cycle progression, CXCR5 expression, and migration were comparable between OX40L(+/+) and OX40L(-/-) mice inoculated with OVA and H. polygyrus. These studies suggest an important role for OX40/OX40L interactions in specifically promoting IL-4 production, as well as associated IgE elevations, in Th2 responses to H. polygyrus. However, OX40L interactions were not required for serum IgG1 elevations, increases in germinal center formation, and Ag-specific Th2 cell expansion and migration to the B cell zone.
Ekkens
Melinda J
MJ
Department of Microbiology and Immunology, Uniformed Services University of the Health Sciences, Bethesda, MD 20814, USA.
Liu
Zhugong
Z
Liu
Qian
Q
Whitmire
Jeannette
J
Xiao
Shiyun
S
Foster
Anthony
A
Pesce
John
J
VanNoy
Jansie
J
Sharpe
Arlene H
AH
Urban
Joseph F
JF
Gause
William C
WC
D000595:Amino Acid Sequence; D000818:Animals; D000947:Antigens, Helminth / Q000276:immunology; D016175:B-Lymphocyte Subsets / Q000276:immunology; D002453:Cell Cycle / Q000235:genetics / Q000276:immunology; D002465:Cell Movement / Q000235:genetics / Q000276:immunology; D019743:Chemokines, CXC / Q000378:metabolism; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D018858:Germinal Center / Q000276:immunology / Q000473:pathology; D006790:Host-Parasite Interactions / Q000235:genetics / Q000276:immunology; D007113:Immunity, Innate / Q000235:genetics; D007117:Immunization, Secondary; D007073:Immunoglobulin E / Q000096:biosynthesis / Q000097:blood; D007074:Immunoglobulin G / Q000096:biosynthesis / Q000097:blood; D007279:Injections, Subcutaneous; D015847:Interleukin-4 / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D007411:Intestinal Diseases, Parasitic / Q000235:genetics / Q000276:immunology*; D008024:Ligands; D008198:Lymph Nodes / Q000276:immunology / Q000473:pathology; D008213:Lymphocyte Activation / Q000235:genetics; D008562:Membrane Glycoproteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D009333:Neck; D009351:Nematospiroides dubius / Q000276:immunology*; D053278:OX40 Ligand; D010047:Ovalbumin / Q000008:administration & dosage / Q000276:immunology; D010446:Peptide Fragments / Q000008:administration & dosage / Q000276:immunology; D054380:Receptors, CXCR5; D019707:Receptors, Chemokine; D018121:Receptors, Cytokine / Q000096:biosynthesis; D053262:Receptors, OX40; D018124:Receptors, Tumor Necrosis Factor; D017206:Strongylida Infections / Q000235:genetics / Q000276:immunology*; D018418:Th2 Cells / Q000276:immunology* / Q000378:metabolism* / Q000473:pathology; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7 / Q000378:metabolism*; D048069:Tumor Necrosis Factors; D015854:Up-Regulation / Q000235:genetics / Q000276:immunology
D000947:Antigens, Helminth; C513179:CXCR5 protein, mouse; D019743:Chemokines, CXC; D018984:Epitopes, T-Lymphocyte; D007074:Immunoglobulin G; D008024:Ligands; D008562:Membrane Glycoproteins; C111390:OVA 323-339; D053278:OX40 Ligand; D010446:Peptide Fragments; D054380:Receptors, CXCR5; D019707:Receptors, Chemokine; D018121:Receptors, Cytokine; D053262:Receptors, OX40; D018124:Receptors, Tumor Necrosis Factor; C505716:TNFRSF4 protein, human; C505717:Tnfrsf4 protein, mouse; C504586:Tnfsf4 protein, mouse; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7; D048069:Tumor Necrosis Factors; D015847:Interleukin-4; D007073:Immunoglobulin E; D010047:Ovalbumin