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Regulatory T cells in transplantation - from preclinical models to clinical study

After exposure to alloantigen in vivo and in vitro, alloantigen reactive immunoregulatory activity is enriched in a population of CD4+ T cells that express high levels of CD25, the α chain of the interleukin-2 receptor, and the transcription factor FOXP3. In vivo, common mechanisms underpin the activity of CD25+CD4+ Treg in adult hosts. We identified a unique role for IFNγ in the functional activity of CD25+CD4+ alloantigen reactive Treg during the development of operational tolerance to donor alloantigens in vivo that is consistent with observations showing that tolerance to alloantigens cannot be induced in the absence of IFNγ [1]. In order to provide proof of concept data for translation of findings in preclinical models to the bedside, we have demonstrated that human regulatory T cells expanded ex vivo can protect human allografts (skin and vessels) from rejection [2, 3].

The identification and characterisation of Treg that can control immune responsiveness to alloantigens has opened up exciting opportunities for new therapies in transplantation.

References

  1. 1.

    Sawitzki B, Kingsley CI, Oliveira V, Karim M, Herber M, Wood KJ: Interferon gamma production by alloantigen reactive CD25+CD4+ regulatory T cells is important for their regulatory function in vivo. Journal of Experimental Medicine. 2005, 201: 1925-1935. 10.1084/jem.20050419.

  2. 2.

    Nadig SN, Wieckiewicz J, Wu DC, Warnecke G, Zhang W, Luo S, et al: In vivo prevention of transplant arteriosclerosis by ex vivo-expanded human regulatory T cells. Nat Med. 2010, 16 (7): 809-813. 10.1038/nm.2154.

  3. 3.

    Issa F, Hester J, Goto R, Nadig SN, Goodacre T, Wood K: Ex vivo-expanded human regulatory T cells prevent the rejection of skin allografts in a humanised mouse model. Transplantation. 2010, 90: 1321-1327. 10.1097/TP.0b013e3181ff8772.

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Correspondence to Kathryn Wood.

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Keywords

  • Public Health
  • Transcription Factor
  • Immune Responsiveness
  • Clinical Study
  • Functional Activity