Regulation of autoimmune diabetes by interleukin 3-dependent bone marrow-derived cells in NOD mice.
Interleukin-3 (IL-3), a multilineage colony stimulating factor, has been shown to augment alloreactive bone marrow-derived suppressor cell activity in vivo and in vitro. The present study examined the effect of IL-3 on autoimmune-mediated diabetes in NOD mice. Administration of IL-3 twice weekly starting at 2-4 weeks of age delayed the onset and reduced the overall incidence of diabetes. Bone marrow cells obtained from IL-3-treated NOD mice protected NOD mice from cyclophosphamide-induced diabetes but failed to prevent adoptively transferred diabetes. In vitro culture of bone marrow cells in medium containing IL-3 produced a Thy-1+CD3epsilonloCD4-CD8-CD25- immature T cell clone which prevented cyclophosphamide-induced diabetes. The cloned cells also effectively delayed the development of diabetes induced by transfer of T cells in adult thymectomized, irradiated, bone marrow-reconstituted NOD mice. These results suggest that IL-3 is capable of regulating extrathymic T cell development from the bone marrow and that these cells mediate strong immunoregulatory function.
Ito
A
A
Cellular and Transplantation Immunology Laboratory, Division of Organ Transplantation, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA, USA.
Aoyanagi
N
N
Maki
T
T
D019264:Adoptive Transfer; D000818:Animals; D015551:Autoimmunity; D001853:Bone Marrow / Q000276:immunology* / Q000473:pathology; D002999:Clone Cells; D003602:Cytotoxicity, Immunologic; D003922:Diabetes Mellitus, Type 1 / Q000209:etiology / Q000276:immunology* / Q000517:prevention & control; D005260:Female; D007165:Immunosuppression Therapy; D066298:In Vitro Techniques; D007377:Interleukin-3 / Q000494:pharmacology*; D051379:Mice; D016688:Mice, Inbred NOD; D011236:Prediabetic State / Q000209:etiology / Q000276:immunology / Q000517:prevention & control; D013601:T-Lymphocytes / Q000276:immunology / Q000473:pathology
D007377:Interleukin-3