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We follow with interest, evidence published in this Journal concerning the sensitivities to apoptosis of effector and regulatory T cells (Treg) in inflammatory bowel disease (IBD), as a possible mechanism of breakdown in self-tolerance.1–4 The persistent and relapsing pattern of IBD might originate from outstanding resistance of human enteric cells to apoptosis5 or excessive apoptosis of Treg.3 Thus, therapeutic approaches aiming to restore enteric immune homeostasis should either delete effector cells or improve Treg survival, though it is unclear whether Treg apoptosis is causative or a consequence of enteric autoimmunity in IBD patients.3 Targeted deletion of effector cells has been achieved with a fusion protein composed of interleukin-2 (IL-2, internalisation moiety) and active caspase-2 (apoptotic molecule), bypassing the apparent defective caspase function in colitogenic cells.6 We reasoned that Treg endowed with enhanced killing activity might significantly attenuate the course of inflammatory colitis by shifting the effector/suppressor balance.
In prior studies, we showed that administration of relatively small numbers of Treg decorated with Fas-ligand (FasL) protein (killer Treg), but not naïve Treg, delays the onset of hyperglycaemia in prediabetic non-obese diabetic …
Contributors All authors contributed to production of the data and preparation of the letter.
Funding This work was supported by grants from the Frankel Trust for Experimental Bone Marrow Transplantation.
Competing interests The SA-FasL protein and ProtEx technology described in this manuscript are licenced from UofL by ApoImmune, Inc, Louisville, KY, in which ESY has significant equity interest in the Company. The other authors disclosed no potential competing interests.
Provenance and peer review Not commissioned; internally peer reviewed.
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