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  • Review Article
  • Published:

Memory T cells in organ transplantation: progress and challenges

Nature Reviews Nephrology volume 12, pages 339–347 (2016)Cite this article

Subjects

Key Points

  • Memory T cells and their ability to generate an anamnestic response are critical for protective immunity, but contribute to allogeneic organ transplant rejection

  • Allospecific memory can be generated through heterologous cross-reactivity and homeostatic proliferation, as well as through prior exposure to allogeneic antigens

  • Inhibitors of calcineurin and mammalian target of rapamycin effectively, but non-specifically, impede memory T-cell responses

  • Co-stimulation blockade inhibits T-cell responses to de novo alloantigen, but does not inhibit allospecific memory T-cell responses

  • Several therapeutic agents that target molecules upregulated on memory T cells have been shown to synergize with co-stimulation blockade to mitigate the effects of memory T cells in organ transplantation

  • Further investigation of memory T cells in transplantation will enhance the application of current immunosuppression therapies, as well as guide the development of novel agents to improve outcomes

Abstract

Antigen-experienced T cells, also known as memory T cells, are functionally and phenotypically distinct from naive T cells. Their enhanced expression of adhesion molecules and reduced requirement for co-stimulation enables them to mount potent and rapid recall responses to subsequent antigen encounters. Memory T cells generated in response to prior antigen exposures can cross-react with other nonidentical, but similar, antigens. This heterologous cross-reactivity not only enhances protective immune responses, but also engenders de novo alloimmunity. This latter characteristic is increasingly recognized as a potential barrier to allograft acceptance that is worthy of immunotherapeutic intervention, and several approaches have been investigated. Calcineurin inhibition effectively controls memory T-cell responses to allografts, but this benefit comes at the expense of increased infectious morbidity. Lymphocyte depletion eliminates allospecific T cells but spares memory T cells to some extent, such that patients do not completely lose protective immunity. Co-stimulation blockade is associated with reduced adverse-effect profiles and improved graft function relative to calcineurin inhibition, but lacks efficacy in controlling memory T-cell responses. Targeting the adhesion molecules that are upregulated on memory T cells might offer additional means to control co-stimulation-blockade-resistant memory T-cell responses.

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Figure 1: Plasticity of memory T cells.
Figure 2: Immunosuppressive agents target molecules that are differentially expressed on naive and memory T cells.

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Authors and Affiliations

  1. Department of Surgery, Emory University School of Medicine, 101 Woodruff Circle, #5101-WMB, Atlanta, 30322, Georgia, USA

    Jaclyn R. Espinosa

  2. Department of Surgery, Duke University School of Medicine, 7690 HAFS Building, Duke North Campus PO Box: 3704, Durham, 27710, North Carolina, USA

    Kannan P. Samy & Allan D. Kirk

Authors
  1. Jaclyn R. Espinosa
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  2. Kannan P. Samy
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  3. Allan D. Kirk
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Contributions

All authors researched the data, made substantial contributions to discussions of the content, wrote the article and reviewed and/or edited the manuscript before submission.

Corresponding author

Correspondence to Allan D. Kirk.

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Competing interests

The authors declare no competing financial interests.

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Espinosa, J., Samy, K. & Kirk, A. Memory T cells in organ transplantation: progress and challenges. Nat Rev Nephrol 12, 339–347 (2016). https://doi.org/10.1038/nrneph.2016.9

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