Wheat protein-induced proinflammatory T helper 1 bias in mesenteric lymph nodes of young diabetes-prone rats.
OBJECTIVE
Type 1 diabetes is the result of an inflammatory T helper 1 (Th1) lymphocyte-mediated beta cell destructive process. The majority of diabetes-prone BioBreeding (BBdp) rats fed wheat protein-based diets, such as NTP-2000, develop type 1 diabetes and display a mild coeliac-like enteropathy. Mesenteric lymph nodes (MLNs), which drain the gut, are the major inductive site where dietary antigens are recognised in the gut-associated lymphoid tissue (GALT). We hypothesised that this compartment could be a site of abnormal wheat protein-induced Th1 cell activation.


METHODS
MLN cells were isolated from BBdp and BB control (BBc) rats that were fed NTP-2000 or a hydrolysed casein (HC)-based diet at ages that pre-date classic insulitis. The inflammatory status, phenotype and proliferation of these cells in response to wheat protein were determined.


RESULTS
The expression ratio of T-bet : Gata3, master transcription factors for Th1 and Th2 cytokines, was increased in the MLN from NTP-2000-fed BBdp rats compared with that from BBc rats, mainly due to decreased Gata3 expression. CD3(+)CD4(+)IFN-gamma(+) T cells were more prevalent in the MLN of wheat-fed BBdp rats, but remained at control levels in BBdp rats fed a diabetes-retardant HC diet. BBdp MLN cells proliferated in response to wheat protein antigens in a specific, dose-dependent manner, and >93% of cells were CD3(+)CD4(+) T cells. This proliferation was associated with a low proportion of CD4(+)CD25(+) T cells and a high proportion of dendritic cells in the MLN of BBdp rats.


CONCLUSIONS
Before insulitis is established, the MLNs of wheat-fed BBdp rats contain an unusually high proportion of Th1 cells that proliferate specifically in response to wheat protein antigens.
Molecular Medicine, Ottawa Health Research Institute, Ottawa, ON K1H 8L6, Canada.
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H
Chakir
D E
DE
Lefebvre
H
H
Wang
E
E
Caraher
F W
FW
Scott
D000818:Animals; D000938:Antigen-Presenting Cells / Q000187:drug effects; D015704:CD4 Antigens / Q000096:biosynthesis; D049109:Cell Proliferation / Q000187:drug effects; D016207:Cytokines / Q000494:pharmacology; D004268:DNA-Binding Proteins / Q000235:genetics; D003920:Diabetes Mellitus / Q000276:immunology*; D004032:Diet; D005434:Flow Cytometry; D050990:GATA3 Transcription Factor; D007202:Indicators and Reagents; D007371:Interferon-gamma / Q000096:biosynthesis; D008198:Lymph Nodes / Q000187:drug effects / Q000276:immunology*; D008643:Mesentery / Q000187:drug effects / Q000276:immunology; D010641:Phenotype; D010940:Plant Proteins / Q000494:pharmacology*; D051381:Rats; D011913:Rats, Inbred BB; D013154:Spleen / Q000166:cytology / Q000187:drug effects; D020825:T-Box Domain Proteins / Q000096:biosynthesis / Q000235:genetics; D018417:Th1 Cells / Q000187:drug effects*; D018418:Th2 Cells / Q000187:drug effects; D015534:Trans-Activators / Q000235:genetics; D014908:Triticum / Q000737:chemistry*
D015704:CD4 Antigens; D016207:Cytokines; D004268:DNA-Binding Proteins; D050990:GATA3 Transcription Factor; D007202:Indicators and Reagents; D010940:Plant Proteins; D020825:T-Box Domain Proteins; D015534:Trans-Activators; D007371:Interferon-gamma