6533b857fe1ef96bd12b3b5b

RESEARCH PRODUCT

Selective targeting of activated T cells in chronic intestinal inflammation

subject

description

Programmed cell death (apoptosis) has been implicated in normal biological processes as well as in the pathology of human diseases.1 The characterisation of genes involved in apoptosis has been pursued intensively and led to the identification of two major classes of genes: the bcl-2 family and the caspase family. Caspases are proteases that cleave their target substrates at specific peptide sequences and during apoptosis the activation of caspases takes place in a cascade fashion, leading to nuclear engulfment and cell death. Thus, caspases represent key functional components of the apoptosis pathway in human cells. Resistance against apoptosis is a key phenomenon in various chronic inflammatory diseases as well as cancer.2–4 In the immune system, it has been shown that T cell resistance against apoptosis may contribute for the perpetuation of inflammatory processes such as seen in patients with inflammatory bowel diseases.5 6 This resistance of T cells against programmed cell death is probably driven by proinflammatory cytokines such as interleukin 6 (IL6).7 However, the functional relevance of T cell resistance against apoptosis is highlighted by the finding that induction of T cell death is likely related to the therapeutic efficacy of anti-tumour necrosis factor (TNF) antibodies in patients with inflammatory bowel diseases. …