Diabetologia. 2003 Aug;46(8):1106-14. Epub 2003 Jul 10.

Pancreatic NOD beta cells express MHC class II protein and the frequency of I-A(g7) mRNA-expressing beta cells strongly increases during progression to autoimmune diabetes.

Walter U, Toepfer T, Dittmar KE, Kretschmer K, Lauber J, Weiss S, Servos G, Lechner O, Scherbaum WA, Bornstein SR, Von Boehmer H, Buer J.

Source

Department of Cellbiology and Immunology, German Research Centre for Biotechnology, Braunschweig, Germany. Ulrich.Walter@med.uni-duesseldorf.de

Abstract

AIMS/HYPOTHESIS:

In the NOD mouse model, attempts to show MHC class II expression by pancreatic beta cells were unsuccessful so far. We readdressed this question by analysing I-A(g7) expression in single pancreatic beta cells.

METHODS:

Single-cell multiplex RT PCR and single-cell immunofluorescence were used to study MHC class II expression in NOD and NOD/SCID beta cells.

RESULTS:

Pancreatic beta cells from NOD mice express the I-A(g7) protein as well as the corresponding mRNA. The frequency of MHC class II mRNA-expressing beta cells is drastically increased during the progression to overt diabetes. MHC class II protein is accumulated intracellularly, and invariant chain is co-expressed. Beta cells from 9- to 10-week-old NOD/SCID mice express MHC class II at the same low frequency as beta cells from 3-week-old NOD mice.

CONCLUSION/INTERPRETATION:

NOD beta cells express I-A(g7) and could be a direct target of autoreactive CD4+ T cells. This MHC class II expression is triggered by infiltrating lymphocytes.

Comment in

To: Walter U, Toepfer T, Dittmar KE et al. (2003) Pancreatic NOD beta cells express MHC class II protein and the frequency of I-A(g7) mRNA-expressing beta cells strongly increases during progression to autoimmune diabetes. Diabetologia 46:1106-1114. [Diabetologia. 2004]
To: Walter U, Toepfer T, Dittmar KE et al. (2003) Pancreatic NOD beta cells express MHC class II protein and the frequency of I-A(g7) mRNA-expressing beta cells strongly increases during progression to autoimmune diabetes. Diabetologia 46:1106-1114.Gray DW. Diabetologia. 2004 Jan; 47(1):143. Epub 2003 Dec 10.

PMID:: 12856083; [PubMed - indexed for MEDLINE]

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To: Walter U, Toepfer T, Dittmar KE et al. (2003) Pancreatic NOD beta cells express MHC class II protein and the frequency of I-A(g7) mRNA-expressing beta cells strongly increases during progression to autoimmune diabetes. Diabetologia 46:1106-1114. [Diabetologia. 2004]
To: Walter U, Toepfer T, Dittmar KE et al. (2003) Pancreatic NOD beta cells express MHC class II protein and the frequency of I-A(g7) mRNA-expressing beta cells strongly increases during progression to autoimmune diabetes. Diabetologia 46:1106-1114.
Gray DW. Diabetologia. 2004 Jan; 47(1):143. Epub 2003 Dec 10.
Thymic positive selection and peripheral activation of islet antigen-specific T cells: separation of two diabetogenic steps by an I-A(g7) class II MHC beta-chain mutant. [J Immunol. 1998]
Thymic positive selection and peripheral activation of islet antigen-specific T cells: separation of two diabetogenic steps by an I-A(g7) class II MHC beta-chain mutant.
Kanagawa O, Vaupel BA, Xu G, Unanue ER, Katz JD. J Immunol. 1998 Nov 1; 161(9):4489-92.
MHC-mismatched islet allografts are vulnerable to autoimmune recognition in vivo. [J Immunol. 2005]
MHC-mismatched islet allografts are vulnerable to autoimmune recognition in vivo.
Kupfer TM, Crawford ML, Pham K, Gill RG. J Immunol. 2005 Aug 15; 175(4):2309-16.
Review Influence of T lymphocytes and major histocompatibility complex class II genes on diabetes susceptibility in the NOD mouse. [Curr Top Microbiol Immunol. 1996]
Review Influence of T lymphocytes and major histocompatibility complex class II genes on diabetes susceptibility in the NOD mouse.
Slattery RM, Miller JF. Curr Top Microbiol Immunol. 1996; 206:51-66.
Review Molecular analysis of the pathogenesis of autoimmune insulitis in NOD mice. [Tohoku J Exp Med. 1994]
Review Molecular analysis of the pathogenesis of autoimmune insulitis in NOD mice.
Koide Y, Kaidoh T, Nakamura M, Yoshida TO. Tohoku J Exp Med. 1994 May; 173(1):157-70.

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Santos Júnior RR, Sartori A, Bonato VL, Coelho Castelo AA, Vilella CA, Zollner RL, Silva CL. Clin Exp Immunol. 2007 Sep; 149(3):570-8. Epub 2007 Jun 22.

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