Initiation of autoimmune diabetes in NOD/Lt mice is MHC class I-dependent.
Animal, Autoimmunity, Diabetes-Mellitus-Experimental: im, Diabetes-Mellitus-Insulin-Dependent: im, Female, Histocompatibility-Antigens-Class-II: im, Mice, Mice-Inbred-NOD, SUPPORT-U-S-GOVT-P-H-S, T-Lymphocytes: im
J Immunol 1997 Apr 15;158(8):3978-86
DK46266/DK/NIDDK, DK51090/DK/NIDDK, DK36175/DK/NIDDK
MHC class II alleles clearly contribute a primary genetic component of susceptibility to autoimmune insulin-dependent diabetes mellitus (IDDM) in nonobese diabetic (NOD) mice. However, IDDM does not occur in NOD mice made MHC class I-deficient by a functionally inactivated beta2-microglobulin allele (beta2m(null)). In the present study the beta2m(null) mutation was used to examine the relative contributions of MHC class I and class II-dependent T cell responses for initiating autoimmune pancreatic beta cell destruction in NOD mice. Splenocytes from diabetic NOD donors transferred IDDM to both lymphocyte-deficient NOD-scid (class I+) and NOD-scid.beta2m(null) mice (class I-). In contrast, splenocytes from young prediabetic NOD donors only transferred IDDM to class I+, but not class I- NOD-scid recipients. However, splenocytes from prediabetic NOD donors did transfer IDDM to NOD-scid.beta2m(null) recipients previously engrafted with class I+, but not class I-, pancreatic islets. CD4+ T cell lines reactive against some syngeneic class I+ targets could be isolated from NOD.beta2m(null) mice. However, NOD.beta2m(null) T cells underwent activation-driven deletion when transferred into class I+ NOD-scid recipients. Hence, the class I autoreactive T cells present in NOD.beta2m(null) donors did not elicit IDDM when transferred into class I+ NOD-scid recipients. Collectively, these results show that autoimmune IDDM in NOD mice is initiated by MHC class I-dependent T cell responses, but this leads to the subsequent activation of additional T cell populations that can mediate pancreatic beta cell destruction in a MHC class I-independent manner.
Serreze, D V.; Chapman, H D.; Varnum, D S.; Gerling, I; Leiter, E H.; and Shultz, L D., " Initiation of autoimmune diabetes in NOD/Lt mice is MHC class I-dependent." (1997). Faculty Research 1990 - 1999. 863.