IFN-gamma affects homing of diabetogenic T cells.
IFN-gamma is a cytokine with pleiotropic functions that participates in immune and autoimmune responses. The lack of IFN-gamma is known to delay the development of autoimmune diabetes in nonobese diabetic (NOD) mice. Splenocytes from diabetic NOD and IFN-gamma knockout (KO) NOD mice transfer diabetes into NOD recipients equally well. However, adoptive transfer of diabetogenic T cells from NOD mice into NOD.IFN-gamma-KO or NOD mice lacking beta-chain of IFN-gamma receptor (NOD.IFN-gammaRbeta-KO) appeared to be much less efficient. We found that IFN-gamma influences the ability of diabetogenic cells to penetrate pancreatic islets. Tracing in vivo of insulin-specific CD8+ T cells has shown that homing of these cells to the islets of Langerhans was affected by the lack of IFN-gamma. While adhesion of insulin-specific CD8+ cells to microvasculature was normal, the diapedesis was significantly impaired. This effect was reversible by treatment of the animals with rIFN-gamma. Thus, IFN-gamma may, among other effects, influence immune and autoimmune responses by supporting the homing of activated T cells.
Savinov
A Y
AY
The Jackson Laboratory, Bar Harbor, ME 04609, USA.
Wong
F S
FS
Chervonsky
A V
AV
D019264:Adoptive Transfer; D000818:Animals; D017951:Antigen Presentation / Q000235:genetics; D002465:Cell Movement / Q000276:immunology*; D003922:Diabetes Mellitus, Type 1 / Q000209:etiology / Q000276:immunology* / Q000473:pathology; D005260:Female; D007275:Injections, Intravenous; D007371:Interferon-gamma / Q000096:biosynthesis / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D007515:Islets of Langerhans / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D017710:Lymphocyte Transfusion; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D016688:Mice, Inbred NOD; D018345:Mice, Knockout; D016513:Mice, SCID; D013154:Spleen / Q000473:pathology / Q000637:transplantation; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000473:pathology
D007371:Interferon-gamma