Adoptive transfer of islet antigen-autoreactive T cell clones to transgenic NOD.Ea(d)mice induces diabetes indicating a lack of I-E mediated protection against activated effector T cells.
Transgenic insertion of the MHC class II Ea(d)gene in NOD mice restores I-E expression and prevents T-cell-mediated autoimmune diabetes (IDDM). The specific molecular and cellular mechanisms responsible for the diabetes resistance of transgenic NOD.Ea(d)mice remain unclear. We adoptively transferred islet antigen-specific T cell clones into NOD and transgenic NOD.Ea(d)mice to evaluate the level of protection provided by I-E expression against activated effector T cells. We have found that neither neonatal or 3-5-week-old I-E-expressing NOD.Ea(d)mice can completely inhibit the diabetogenic activities of activated islet antigen-specific T cell clones. These data indicate that Ealpha protein expression in NOD antigen presenting cells (APC) does not reduce islet autoantigen presentation in the context of I-A(g7)below the threshold required for stimulation of effector/memory diabetogenic T cells. Our results suggest that the mechanism of Ealpha protein-mediated diabetes resistance in NOD mice may be "antigen ignorance," in which the quantity of islet autoantigens presented in the context of I-A(g7)by APC is reduced below the threshold required to activate nai;ve islet antigen-specific T cells.
Roberts
Samantha A
SA
Department of Biology, Wittenberg University, Ward St. at N. Wittenberg Ave., Springfield, OH 45501-0720, USA.
Barbour
Gene
G
Matarrese
Marissa R
MR
Mason
David L
DL
Leiter
Edward H
EH
Haskins
Kathryn
K
Hanson
Matthew S
MS
D019264:Adoptive Transfer; D000818:Animals; D000831:Animals, Newborn; D001324:Autoantigens / Q000276:immunology*; D002999:Clone Cells; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology*; D000949:Histocompatibility Antigens Class II / Q000235:genetics / Q000378:metabolism*; D007515:Islets of Langerhans / Q000276:immunology*; D008213:Lymphocyte Activation; D051379:Mice; D016688:Mice, Inbred NOD; D008822:Mice, Transgenic; D013601:T-Lymphocytes / Q000276:immunology* / Q000637:transplantation
D001324:Autoantigens; D000949:Histocompatibility Antigens Class II; C024138:I-E-antigen