The roles of soluble osteopontin using osteopontin-transgenic mice in vivo: proliferation of CD4+ T lymphocytes and the enhancement of cell-mediated immune responses.
We generated transgenic mice expressing osteopontin (OPN) under the control of the alpha(1)-antitrypsin promoter. These mice (OPN-T mice) expressed OPN mRNA in liver and kidney, and released a large amount of plasma OPN, which increased after stimulation with turpentine oil. Before sensitization, the number of CD4+ T cells in lymph nodes was significantly higher in OPN-T than nontransgenic mice, and that in spleen was slightly higher, whereas that of CD8+ T cells was no different between OPN-T and nontransgenic mice. After sensitization, the CD4+ T cell numbers in spleen increased significantly, while there were almost no changes in the CD8+ T cells in lymph nodes and spleen. The intensity of contact hypersensitivity responses to 2,4-dinitrofluorobenzene (DNFB) was obviously enhanced in OPN-T mice. In the delayed-type hypersensitivity (DTH) model elicited by DNFB, the number of CD8+ T cells among DNFB-2,4,6-trinitrobenzenesulfonic acid (TNBS)-peritoneal exudate cells was significantly higher in OPN-T than nontransgenic mice, while there was almost no difference in that of CD4+ T cells. Adoptive transfer experiments revealed that the enhanced reactivity is carried by CD4+ and CD8+ T cells, respectively, although the ability of transferring DTH was significantly lower in CD8+ than in CD4+ T cells. The enhancement of CD8+ T cell migration was observed in OPN-T mice. These results suggest that OPN induces a proliferation of effector CD4+ and CD8+ cells in cell-mediated reactions and plays a role in the migration of CD8+ T cells.
Higuchi
Yasunori
Y
Department of Pathology, Oita Medical University, Hasama-machi, Oita, Japan. higuchi@oita-med.ac.jp
Tamura
Yoichi
Y
Uchida
Tomohisa
T
Matsuura
Keiko
K
Hijiya
Naoki
N
Yamamoto
Shunsuke
S
D019264:Adoptive Transfer; D000818:Animals; D015152:Blotting, Northern; D015153:Blotting, Western; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002465:Cell Movement / Q000276:immunology; D003877:Dermatitis, Contact / Q000276:immunology; D005260:Female; D005434:Flow Cytometry; D007111:Immunity, Cellular; D008198:Lymph Nodes / Q000166:cytology / Q000276:immunology; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D053495:Osteopontin; D012795:Sialoglycoproteins / Q000235:genetics / Q000276:immunology*; D013154:Spleen / Q000166:cytology / Q000276:immunology
D012795:Sialoglycoproteins; C506896:Spp1 protein, mouse; D053495:Osteopontin