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.
Chakir
H
H
Molecular Medicine, Ottawa Health Research Institute, Ottawa, ON K1H 8L6, Canada.
Lefebvre
D E
DE
Wang
H
H
Caraher
E
E
Scott
F W
FW
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