T cell receptor repertoire and mitotic responses of lamina propria T lymphocytes in inflammatory bowel disease.
Human intestinal lamina propria T lymphocytes (LPL-T) physiologically exhibit minimal proliferation in response to antigen receptor stimulation in vitro. This is thought to occur as a consequence of regulatory influences which are exerted by the mucosal microenvironment. The present study is aimed at investigating whether proliferative responses of intestinal LPL-T to antigen receptor stimulation are altered in patients with inflammatory bowel disease. Accordingly, proliferative responses of LPL-T in patients with Crohn's disease and ulcerative colitis to stimulation with CD3 MoAb plus IL-2 were examined and compared with controls. In addition, T cell receptor (TCR) repertoires of LPL-T and peripheral blood T lymphocytes were determined by indirect immunofluorescence using a panel of 11 TCR V beta specific antibodies. In most patients with inflammatory bowel disease, LPL-T showed enhanced proliferation to antigen receptor stimulation compared with controls. Moreover, perhaps as a consequence, an enhanced frequency of in vivo preactivated T cells was seen as judged from an increased spontaneous proliferative response to low concentrations of exogenous IL-2. LPL-T and peripheral blood T lymphocytes exhibited similar percentages of TCR V beta gene usage both in controls and in patients. In summary, polyclonal activation of LPL-T due to impairment of local adjustment, i.e. insufficient down-regulation of TCR/CD3-dependent signalling processes, may contribute to the pathogenesis of inflammatory bowel disease.
Qiao
L
L
German Cancer Research Centre, Heidelberg.
Golling
M
M
Autschbach
F
F
Schürmann
G
G
Meuer
S C
SC
D000293:Adolescent; D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal; D003093:Colitis, Ulcerative / Q000276:immunology; D003424:Crohn Disease / Q000276:immunology; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D015212:Inflammatory Bowel Diseases / Q000276:immunology*; D007376:Interleukin-2 / Q000502:physiology; D007413:Intestinal Mucosa / Q000166:cytology / Q000276:immunology*; D008213:Lymphocyte Activation; D008297:Male; D008875:Middle Aged; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*
D000911:Antibodies, Monoclonal; D007376:Interleukin-2; D016693:Receptors, Antigen, T-Cell, alpha-beta