Inflammatory bowel diseases (IBDs) such as Crohn’s disease and ulcerative colitis are the result of an imbalanced mucosal T cell response. Despite the identification of a genetic susceptibility region in the NOD2/CARD15 (nucleotide-binding oligomerisation domain 2/caspase recruitment domain 15) gene, the aetiology is still unclear. Thus, the hunt for disease-initiating factors such as defects in the mucosal barrier or pathogenic microorganisms is ongoing. By contrast, the immunopathogenesis in IBDs is better understood. The identification of cytokines that are involved in T cell and monocyte signalling led to specific therapeutic concepts. Recent data have clearly shown that the most powerful therapeutic approaches inhibit T cell survival by inducing apoptosis. The efficacy of anti-tumour necrosis factor (TNF) strategies was proved to be at least partially due to its ability to induce apoptosis in T cells and monocytes. Furthermore, other powerful anticytokine strategies—namely, anti-interleukin (IL)12 and anti-IL6 antibodies, which are currently tested in clinical trials—also inhibit antiapoptotic pathways in T cells. Recently, the well-established immunosuppressive drug azathioprine was identified as blocking antiapoptotic pathways in T cells. Data from these studies underline the pivotal role of lymphocyte apoptosis in the regulation of mucosal immune balance.

BACKGROUND

A role for apoptosis or programmed cell death is well established in the context of inflammation or cancer. Decades ago, cell death was described as a phenomenon in the normal development of vertebrates.¹ In 1965, Kerr and colleagues observed the cell death of hepatocytes after portal branch ligation. In this experimental setting, cell death was attributed to necrosis with concomitant inflammatory processes, but a different type of cell death also occurred in scattered individual cells with shrunken nuclei. In contrast with necrosis, evidence suggested no lysosomal rupture or inflammation.² Some years later, the nuclear masses were found to be membrane-enclosed bodies containing pieces of condensed DNA (chromatin) …