Trends in Immunology
OpinionRegulation of T-cell apoptosis in inflammatory bowel disease: to die or not to die, that is the mucosal question
Section snippets
Regulation of apoptosis of lamina propria T cells via active and passive mechanisms
Immune responses in the mucosa are frequently characterized by major expansions of antigen-specific T cells that have potent effector function 1., 8., 9., 10.. Although this might be important for host defense, it might also lead to effector cell populations with substantial autoreactivity and the capacity to cause mucosal inflammation. To deal with this latter possibility, the mucosal immune system has evolved several strategies for the control of mucosal immune responses. Among these is the
Apoptosis of lamina propria CD4+ T cells in the normal and inflamed gut
As most T cells in the lamina propria (LP) express memory cell markers such as CD45RO (Ref. 3), the activation-induced cell death might be very important to downregulate effector cell function and cytokine production in the gut. Interestingly, memory T cells are known to express Fas constitutively at high levels 13. In the unstimulated state, (that is, prior to TCR stimulation), LP T cells exhibit increased susceptibility to Fas-mediated apoptosis as compared with unstimulated peripheral-blood
IL-12 and apoptosis
Administration of a neutralizing anti-IL-12 antibody to mice with trinitrobenzene sulfonic acid (TNBS)-induced colitis, a T helper 1 (Th1) -mediated inflammation replete with cells producing large amounts of interferon-γ (IFN-γ), IL-12 and TNF-α, is followed after two days by the appearance of apoptotic (terminal deoxynucleotidyltransferase-mediated UTP end-labeling positive, TUNEL+) CD4+ cells at the site of inflammation in the colon 8. This induction of T-cell apoptosis is followed by the
Concluding remarks
Apoptosis of LP T cells appears to be critical in the downregulation of the mucosal immune response and in the elimination of reactive clones. Whereas normal LP T cells exhibit an enhanced susceptibility to Fas-mediated apoptosis 16, Crohn's disease is associated with a resistance of LP T cells against multiple apoptotic pathways 6., 18., 19.. Such defective apoptosis may be a key factor for inappropriate T-cell accumulation and in the perpetuation of chronic mucosal inflammation in IBD (Fig. 3
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2023, Transplant ImmunologyCitation Excerpt :Ample evidence has demonstrated that interleukin-6 (IL-6) plays an important role in the pathogenesis of UC [30–32]. IL-6 contributes to promoting T-cell survival and apoptosis resistance in inflamed tissue [33,34]. It also supports the survival of intestinal epithelial cells [35,36] and plays an essential role in the immune phenotype of regulatory T cells toward inflammatory cells [37].
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