GIF inhibits Th effector generation by acting on antigen-presenting B cells

Citation
K. Sugie et Jy. Huang, GIF inhibits Th effector generation by acting on antigen-presenting B cells, J IMMUNOL, 166(7), 2001, pp. 4473-4480
Citations number
33
Categorie Soggetti
Immunology
Journal title
JOURNAL OF IMMUNOLOGY
ISSN journal
00221767 → ACNP
Volume
166
Issue
7
Year of publication
2001
Pages
4473 - 4480
Database
ISI
SICI code
0022-1767(20010401)166:7<4473:GITEGB>2.0.ZU;2-G
Abstract
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 secr etion of IgG1 and IgE induced by LPS and IL-4. To examine the effect on cog nate T-B interaction, GIF was added to low-density B cells from MD4 transge nic (Tg) mice, which express B cell receptor specific for hen egg lysozyme (HEL). The B cells were subsequently pulsed with HEL-OVA conjugate and cult ured 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 nai ve T cells and rendered them hyporesponsive to antigenic restimulation, res ulting in 50-95% reduction of IL-4 and IFN-gamma secretion upon restimulati on with Ag. GIF dramatically inhibited Th effector generation when it was a dded 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 effectiv e when B cells from MD4 Tg mice were pulsed with HEL-OVA than when they wer e pulsed with OVA. This cytokine did not affect Th effector generation when B cells or irradiated splenocytes pulsed with OVA(323-339) peptide stimula ted 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.