CD4+ T-cell population mediates development of inflammatory bowel disease in T-cell receptor alpha chain-deficient mice.
OBJECTIVE
Increase of T cells expressing CD4 and T-cell receptor (TCR) alpha- beta+ (beta[dim]) was observed in the mucosal and peripheral lymphoid tissues of TCR alpha-/- mice with inflammatory bowel disease (IBD). The aim of this study was to characterize the CD4+ TCR alpha-beta+ T cells.


METHODS
Cytokine production, TCR V beta usage, and helper function for Peyer's patch B cells by the CD4+ TCR alpha-beta+ T cells were assessed.


RESULTS
The CD4+ TCR alpha-beta+ T cells purified from mesenteric lymph nodes and lamina propria of the intestine of IBD mice exclusively produced interleukin 4, used selected subsets (V beta6, V beta8, V beta14, and V beta15) of TCR, and massively proliferated after stimulation with staphylococcal enterotoxin B. Addition of the CD4+ TCR alpha-beta+ T cells to Peyer's patch B-cell cultures markedly enhanced immunoglobulin (Ig) A, IgG, and IgM antibody responses. Furthermore, depletion of the TCR alpha-beta+ T cells with monoclonal antibody against TCR beta chain completely suppressed the onset of IBD and polyclonal B-cell activation in the TCR alpha-/- mice.


CONCLUSIONS
These findings suggest the CD4+ TCR alpha-beta+ T cells-mediated development of IBD in TCR alpha-/- mice.
Takahashi
I
I
Department of Oral Microbiology, Faculty of Dentistry, Research Institute for Microbial Diseases, Osaka University, Suita-Osaka, Japan.
Kiyono
H
H
Hamada
S
S
D000818:Animals; D015704:CD4 Antigens / Q000378:metabolism*; D004195:Disease Models, Animal; D015212:Inflammatory Bowel Diseases / Q000209:etiology / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism*; D013154:Spleen / Q000378:metabolism; D013601:T-Lymphocytes / Q000378:metabolism*
D015704:CD4 Antigens; D011948:Receptors, Antigen, T-Cell