Peripheral cell-mediated immune response to mycobacterial antigens in inflammatory bowel disease.
A mycobacterial etiology has been proposed in Crohn's disease (CD). We have sought evidence of increased or modified T lymphocyte immune responses to Mycobacterium tuberculosis and Myco, paratuberculosis in patients with CD (n = 13), compared with ulcerative colitis (UC; n = 17) and controls (n = 17). Peripheral blood cells were cultured with phytohaemagglutinin (positive mitogen control), mycobacterial purified protein derivative (PPD) preparations, lysates, column fractions and whole, heat-killed bacteria. Responses of T cells and T cell subsets were assessed by expression of activation markers (CD25, CD69), coupled with blastogenesis assays (3H-thymidine uptake) and estimates of proliferation. Virtually all patients responded to Myco. paratuberculosis and Myco. tuberculosis antigens. There were no significant differences between patient groups, although there was a very high overall correlation (r = 0.95; P < 0.0001) between responses to the two mycobacterial species. Most of the activation and proliferative responses resided in the CD4+ (T helper) subset. Although up to 15% of CD8+ (suppressor/cytotoxic) cells also became activated, the CD8+ cells did not proliferate subsequently. Cells expressing the alternate gamma delta form of the T cell receptor (TCR gamma delta+) did not activate or proliferate in response to mycobacterial antigens. There were no differences in any of these parameters between patient groups. We conclude that there is no specific increase or alteration in cell-mediated anti-mycobacterial immunity in inflammatory bowel disease (IBD). Thus our data do not support a mycobacterial etiopathology of Crohn's disease.
Division of Medicine, Research School of Medicine, St Jame's University Hospital, Leeds, UK.
D S
DS
Rowbotham
P D
PD
Howdle
L K
LK
Trejdosiewicz
D000328:Adult; D000368:Aged; D000942:Antigens, Bacterial / Q000276:immunology*; D005260:Female; D006801:Humans; D007111:Immunity, Cellular; D016130:Immunophenotyping; D015212:Inflammatory Bowel Diseases / Q000276:immunology*; D008213:Lymphocyte Activation; D008297:Male; D008875:Middle Aged; D009161:Mycobacterium / Q000276:immunology*; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000032:analysis; D013601:T-Lymphocytes / Q000276:immunology
D000942:Antigens, Bacterial; D016692:Receptors, Antigen, T-Cell, gamma-delta