期刊
CURRENT OPINION IN ORGAN TRANSPLANTATION
卷 15, 期 4, 页码 411-415出版社
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1097/MOT.0b013e32833b7929
关键词
inflammation; regulatory T cells; Th17 cells
资金
- National Institutes of Health [PPG U19 DK080652, P01 AI041521, P01 AI073748, 1F32AI084373-01]
- Juvenile Diabetes Research Foundation [4-2004-368, 1-2007-524]
Purpose of review Inflammation of the allograft, occurring as a consequence of hypoxia and ischemia/reperfusion injury, adversely influences short-term and long-term transplant outcomes. Thus far, imbalance of tissue-protective Treg and tissue-destructive Th17 cells has been confirmed in a number of tissue-inflammatory states, including autoimmune disease. Hence, benefits of tilting Treg-Th17 equilibrium toward dominance of Tregs may promote transplant tolerance. Recent findings Adverse graft inflammation creates extreme resistance to the induction of donor-specific tolerance. Proinflammatory cytokines, when abundantly expressed within the graft and draining lymph nodes, prevent commitment of donor-activated T cells into graft-protective, T-regulatory phenotype, while fostering generation of donor-reactive Th1, Th2 or Th17 effector subsets. In addition, the inflammatory milieu may destabilize the program of both natural and induced Tregs, converting them into inflammatory, effector-like phenotypes. Therefore permanent, Treg-dependent acceptance of an allograft may not be achieved without limiting adverse tissue inflammation. Summary Balance of graft-protective regulatory and graft-destructive effector T cells largely depends on the balance of proinflammatory and anti-inflammatory cytokines in the milieu, in which donor-directed T-cell response occurs. In the absence of proinflammatory cytokines, the constitutive expression of TGF-beta may guide recipient T cells into a tissue-protective, pro-tolerant mode. Therefore, targeting adverse tissue inflammation may represent a powerful means to tilt antidonor immunity towards tolerance.
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