title: Suppression of the bacterial antigen-specific T cell response and the dendritic cell migration to the lymph nodes by osteopontin.
abstract: Osteopontin (OPN) has been reported to enhance the interferon (IFN)-gamma-producing Th1-type T cell response through the induction of interleukin (IL)-12 and the suppression of IL-10. We therefore investigated whether OPN could enhance Th1 induction by vaccination against bacterial antigen in vivo. Unexpectedly, the co-inoculation of OPN suppressed the induction of IFN-gamma-producing CD4(+) T cells and T cell proliferative response after the subcutaneous heat-killed Listeria monocytogenes(HKLM) immunization. These results suggest that OPN down-regulates T cell priming. Since dendritic cells (DC) play a pivotal role in T cell priming, we next analyzed the effects of OPN on DC. The addition of OPN into the culture of either bone marrow-derived immature DC or an immature DC line JAWSII showed no effects on the expression of MHC class II, CD80, and CD86 molecules before and after HKLM stimulation. Consistently, in vitro OPN-treated DC showed a normal antigen-presenting function to an established Listeria-specific Th1-type T cells. However, when the DC were transferred into the footpad with HKLM and OPN, the migration of the transferred DC into the regional LN was suppressed in comparison to the DC transferred with HKLM alone. Furthermore, the addition of OPN into the culture of the DC line and HKLM severely suppressed the HKLM-induced expression of CCR7 chemokine receptor which is an important factor in the migration of DC into LN. All the results suggest the existence of an OPN-mediated negative feedback mechanism in the T cell immune response through the regulation of DC migration.
authors.affiliation: Molecular Microbiology Group, Center of Molecular Biosciences, University of the Ryukyus, Okinaya, Japan.
authors.forename: Mst Dilara
authors.initials: MD
authors.lastname: Begum
authors.forename: Masayuki
authors.initials: M
authors.lastname: Umemura
authors.forename: Shigeyuki
authors.initials: S
authors.lastname: Kon
authors.forename: Ayano
authors.initials: A
authors.lastname: Yahagi
authors.forename: Satoru
authors.initials: S
authors.lastname: Hamada
authors.forename: Kiyotetsu
authors.initials: K
authors.lastname: Oshiro
authors.forename: Kazuyo
authors.initials: K
authors.lastname: Gotoh
authors.forename: Akira
authors.initials: A
authors.lastname: Nishizono
authors.forename: Toshimitsu
authors.initials: T
authors.lastname: Uede
authors.forename: Goro
authors.initials: G
authors.lastname: Matsuzaki
mesh_terms: D000818:Animals; D000942:Antigens, Bacterial / Q000276:immunology*; D000954:Antigens, Surface / Q000032:analysis; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D002460:Cell Line; D002465:Cell Movement; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000276:immunology*; D005260:Female; D005434:Flow Cytometry; D007371:Interferon-gamma / Q000096:biosynthesis; D018664:Interleukin-12 / Q000096:biosynthesis; D008087:Listeria / Q000276:immunology; D008198:Lymph Nodes / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D053495:Osteopontin / Q000276:immunology*; D054400:Receptors, CCR7; D019707:Receptors, Chemokine / Q000235:genetics
chemical_list: D000942:Antigens, Bacterial; D000954:Antigens, Surface; C515371:Ccr7 protein, mouse; D054400:Receptors, CCR7; D019707:Receptors, Chemokine; D053495:Osteopontin; D018664:Interleukin-12; D007371:Interferon-gamma