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

• Published in: Journal of autoimmunity Vol. 21; no. 2; pp. 139 - 147
• Main Authors: Roberts, Samantha A, Barbour, Gene, Matarrese, Marissa R, Mason, David L, Leiter, Edward H, Haskins, Kathryn, Hanson, Matthew S
• Format: Journal Article
• Language: English
• Published: England 01.09.2003
• Subjects: Adoptive Transfer; Animals; Animals, Newborn; Autoantigens - immunology; Clone Cells; Diabetes Mellitus, Type 1 - immunology; Histocompatibility Antigens Class II - genetics; Histocompatibility Antigens Class II - metabolism; Islets of Langerhans - immunology; Lymphocyte Activation; Mice; Mice, Inbred NOD; Mice, Transgenic; T-Lymphocytes - immunology; T-Lymphocytes - transplantation
• ISSN: 0896-8411
• DOI: 10.1016/S0896-8411(03)00090-8

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.