Bacterial superantigens and T cell receptor beta-chain-bearing T cells in the immunopathogenesis of ulcerative colitis.
Ulcerative colitis (UC) is a chronic relapsing-remitting inflammatory bowel disease (IBD) that affects the colon and the rectum producing debilitating symptoms, which impair ability to function and quality of life. The aetiology of IBD is incompletely understood, but within the lymphocyte population, specific T cell subsets are known to be major factors in the development of intestinal immune pathology while different subsets are essential regulators, controlling IBD. Hence, IBD is thought to reflect dysregulated T cell behaviour. This study was to investigate if the normal molecular configuration of the T cell receptor (TCR) repertoire is compromised in patients with UC. The percentage of T cell-bearing beta-chain 4 (TCRBV4) was high in patients with UC, and T cells showed polyclonal expansion in the presence of bacterial superantigens (SA) such as streptococcal mitogenic exotoxin Z-2 (SMEZ-2), indicating that bacterial SA promote specific TCRBV family expansion. Further, in patients with UC, the duration of UC was significantly longer in patients with skewed TCRBV4 compared with patients without TCRBV4 skewing, suggesting that long-term exposure to bacterial SA such as SMEZ-2 might promote systemic immune disorders like the remission-relapsing cycles seen in patients with UC. In conclusion, our observations in this study support the perception that the systemic activation of T cells by enteric bacterial SA might lead to a dysregulated, but exuberant immune activity causing the remission and flare-up cycle of mucosal inflammation in patients with UC. Future studies should strengthen our findings and increase understanding on the aetiology of IBD.
Shiobara
N
N
Department of Rheumatology and Clinical Immunology, Clinical Research Center for Allergy and Rheumatology, National Sagamihara Hospital, Kanagawa, Japan. n-shiobara@sagamihara-hosp.gr.jp
Suzuki
Y
Y
Aoki
H
H
Gotoh
A
A
Fujii
Y
Y
Hamada
Y
Y
Suzuki
S
S
Fukui
N
N
Kurane
I
I
Itoh
T
T
Suzuki
R
R
D000293:Adolescent; D000328:Adult; D000942:Antigens, Bacterial / Q000097:blood / Q000276:immunology*; D001426:Bacterial Proteins / Q000276:immunology; D001427:Bacterial Toxins / Q000276:immunology; D049109:Cell Proliferation; D003093:Colitis, Ulcerative / Q000276:immunology*; D004768:Enterotoxins / Q000276:immunology; D005098:Exotoxins / Q000276:immunology; D005260:Female; D005838:Genotype; D006684:HLA-DR Antigens / Q000235:genetics; D059811:HLA-DRB1 Chains; D006801:Humans; D018928:Immunity, Mucosal; D007413:Intestinal Mucosa / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology; D008297:Male; D008875:Middle Aged; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000032:analysis*; D013301:Streptolysins / Q000276:immunology; D018089:Superantigens / Q000097:blood / Q000276:immunology*; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D013997:Time Factors
D000942:Antigens, Bacterial; D001426:Bacterial Proteins; D001427:Bacterial Toxins; D004768:Enterotoxins; D005098:Exotoxins; D006684:HLA-DR Antigens; D059811:HLA-DRB1 Chains; D016693:Receptors, Antigen, T-Cell, alpha-beta; D013301:Streptolysins; D018089:Superantigens; C030107:enterotoxin F, Staphylococcal; C107894:mitogenic exotoxin Z protein, Streptococcus; C025964:streptolysin O