GIF inhibits Th effector generation by acting on antigen-presenting B cells.
Glycosylation-inhibiting factor (GIF) is a 13-kDa cytokine secreted from T cells. Administration of bioactive recombinant GIF inhibits IgG1 and IgE Ab responses in vivo. Treatment of B cells with the cytokine reduces the secretion of IgG1 and IgE induced by LPS and IL-4. To examine the effect on cognate T-B interaction, GIF was added to low-density B cells from MD4 transgenic (Tg) mice, which express B cell receptor specific for hen egg lysozyme (HEL). The B cells were subsequently pulsed with HEL-OVA conjugate and cultured with OVA-specific naive CD4 T cells from DO11.10 Tg mice. Treatment of Ag-presenting B cells with GIF reduced expansion and IL-2 secretion of naive T cells and rendered them hyporesponsive to antigenic restimulation, resulting in 50--95% reduction of IL-4 and IFN-gamma secretion upon restimulation with Ag. GIF dramatically inhibited Th effector generation when it was added to B cells before pulsing with HEL-OVA, whereas it showed little to no effect when added after B cells were pulsed with Ag. GIF was more effective when B cells from MD4 Tg mice were pulsed with HEL-OVA than when they were pulsed with OVA. This cytokine did not affect Th effector generation when B cells or irradiated splenocytes pulsed with OVA(323--339) peptide stimulated naive DO11.10 T cells. Confocal microscopy revealed that GIF inhibited internalization of HEL by B cells from MD4 Tg mice. Therefore, the cytokine may regulate early steps of Ag presentation involving B cell receptors to diminish Th effector generation from naive CD4 T cells.
Division of Allergy, La Jolla Institute for Allergy and Immunology, San Diego, CA 92121, USA. ksugie@liai.org
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D000818:Animals; D017951:Antigen Presentation; D000938:Antigen-Presenting Cells / Q000276:immunology* / Q000378:metabolism; D001402:B-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology; D002454:Cell Differentiation / Q000276:immunology; D002478:Cells, Cultured; D003545:Cysteine / Q000235:genetics / Q000378:metabolism; D006031:Glycosylation; D006131:Growth Inhibitors / Q000494:pharmacology; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D007399:Interphase / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology*; D008222:Lymphokines / Q000235:genetics / Q000494:pharmacology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009113:Muramidase / Q000276:immunology / Q000378:metabolism; D010047:Ovalbumin / Q000276:immunology / Q000378:metabolism; D010455:Peptides / Q000276:immunology / Q000378:metabolism; D029584:Prostatic Secretory Proteins; D011947:Receptors, Antigen, B-Cell / Q000502:physiology; D011994:Recombinant Proteins / Q000494:pharmacology; D006377:T-Lymphocytes, Helper-Inducer / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D018418:Th2 Cells / Q000276:immunology / Q000378:metabolism
D006131:Growth Inhibitors; D007166:Immunosuppressive Agents; D008222:Lymphokines; D010455:Peptides; D029584:Prostatic Secretory Proteins; D011947:Receptors, Antigen, B-Cell; D011994:Recombinant Proteins; C043076:beta-microseminoprotein; C013059:immunoglobulin-binding factors; D010047:Ovalbumin; D009113:Muramidase; D003545:Cysteine