Human CD4+CD25+ regulatory T cells inhibit the differentiation of osteoclasts from peripheral blood mononuclear cells.
Regulatory T cell (Treg) is a subset of CD4+ T lymphocytes expressing CD25 with immunosuppressive activity. However the function of Tregs onto osteoclastogenesis remains unknown. We investigated the effect and regulatory mechanism of Treg focusing on osteoclastogenesis from PBMCs. Tregs were isolated from PBMCs by magnetic cell sorting-column and analyzed by flow cytometry. RT-PCR was performed to identify Foxp3 mRNA. Using PBMCs and Tregs coculture system, we could find that Tregs inhibited osteoclasts differentiation from PBMCs and reduced the resorbed areas on pit assay (p <0.01). This suppression of osteoclast differentiation was cytokine-dependent, not cell-to-cell direct contact proved by Transwell system. Tregs-induced osteoclast differentiation was blocked by anti-TGF-beta or anti-IL-4 antibody treatment. These results suggest that Tregs inhibit osteoclast differentiation from PBMCs in a cytokine-dependent manner, not by cell-to-cell contact manner and that TGF-beta and IL-4 may be the key cytokines for this suppressive function of Tregs.
Kim
Yong Gil
YG
Division of Rheumatology, Department of Internal Medicine, University of Ulsan College of Medicine, Asan Medical Center, 388-1 Pungnap-dong, Songpa-gu, Seoul 138-736, Republic of Korea.
Lee
Chang-Keun
CK
Nah
Seong-Su
SS
Mun
Se Hwan
SH
Yoo
Bin
B
Moon
Hee-Bom
HB
D015704:CD4 Antigens / Q000276:immunology*; D002450:Cell Communication / Q000276:immunology; D002454:Cell Differentiation; D002478:Cells, Cultured; D018920:Coculture Techniques; D006801:Humans; D053645:Interleukin-2 Receptor alpha Subunit / Q000276:immunology*; D007963:Leukocytes, Mononuclear / Q000166:cytology* / Q000276:immunology; D010010:Osteoclasts / Q000166:cytology* / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000166:cytology* / Q000276:immunology*
D015704:CD4 Antigens; D053645:Interleukin-2 Receptor alpha Subunit