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Post transplant CMV-specific T-cell immune reconstitution in the absence of global T-cell immunity is associated with a high risk of subsequent virus reactivation

Bone Marrow Transplantation volume 50, pages 315–316 (2015)Cite this article

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It is well established that impaired T-cell immune reconstitution is a major risk factor for CMV reactivation following allogeneic HSCT (allo-HSCT).1, 2 Results of immune monitoring studies have generally shown that CMV-specific T-cell immune reconstitution is associated with the spontaneous resolution of CMV viraemia3 and protection from recurrent or complicated CMV reactivation.2, 3, 4 However, unlike solid-organ transplantation, the relationship between CMV-specific immune reconstitution and protection from a first episode of CMV reactivation is unclear in allo-HSCT with some5, 6 but not all2, 7 studies showing protection. As CMV-specific T-cell immune reconstitution is influenced by both homoeostatic proliferation and antigen-driven expansion, we hypothesise that the predictive value of CMV-specific immune monitoring can be improved if these contrasting driving forces can be separated. In this report, we show that the selective reconstitution of CMV-specific immunity ahead of global T-cell immune reconstitution is associated with a significantly higher risk of subsequent CMV reactivation than CMV-specific immune reconstitution that is concordant with global immune reconstitution.

We recently reported the results of a prospective study where weekly CMV-specific immune monitoring was performed using a whole-blood functional assay, QuantiFERON-CMV (Cellestis, Carnegie, VIC, Australia),8 which measures IFN-γ secretion in 1 mL of whole blood in response to 23 CMV peptide epitopes representing diverse MHC class I alleles.9 This assay incorporates a phytohaemagglutinin-treated sample, which measures mitogen response and serves as a positive assay control. In allo-HSCT, where patients are often lymphopenic or have impaired lymphocyte function, the mitogen response correlates with lymphocyte count.8 Although IFN-γ secretion alone does not capture all T-cell activity, the mitogen response provides some indication of global T-cell response as a context for CMV-specific immune reconstitution. Here, we present additional analysis on our previously published study8 and show that CMV-specific immune reconstitution follows two patterns, which are distinguishable by their concordance or otherwise with mitogen response and these two patterns are associated with divergent risks for CMV reactivation.

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Acknowledgements

S-KT is supported by the Australian National Health and Medical Research Council (NH&MRC) Early Career Clinical Fellowship and a Leukaemia Foundation of Australia Clinical Fellowship. RK is supported by an NH&MRC Senior Principal Research Fellowship. GRH is supported by an NH&MRC Australia Fellowship. MPD is supported by an NH&MRC Senior Research Fellowship. DC is supported by a UNSW Vice-Chancellor’s Fellowship.

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Authors and Affiliations

  1. QIMR Centre for Immunotherapy and Vaccine Development and Tumour Immunology Laboratory, QIMR Berghofer Medical Research Institute, Herston, Queensland, Australia

    S-K Tey & R Khanna

  2. Department of Haematology and Bone Marrow Transplantation, Royal Brisbane and Women’s Hospital, Herston, Queensland, Australia

    S-K Tey, G R Hill, G A Kennedy & S T Durrant

  3. School of Medicine, University of Queensland, Herston, Queensland, Australia

    S-K Tey & G A Kennedy

  4. Bone Marrow Transplant Laboratory, QIMR Berghofer Medical Research Institute, Herston, Queensland, Australia

    S-K Tey & G R Hill

  5. Complex Systems in Biology Group, Centre for Vascular Research, UNSW Australia, Kensington, New South Wales, Australia

    M P Davenport & D Cromer

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  1. S-K Tey
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Corresponding author

Correspondence to S-K Tey.

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Competing interests

RK holds an international patent on CMV epitopes, which are included in the QuantiFERON-CMV kit. These epitopes are licensed to Cellestis Inc. for their inclusion in the QuantiFERON-CMV kit. International Patent on Human Cytomegalovirus Immunotherapy (Inventors listed: RK), granted and maintained in the USA (patent No. 7524503), Australia (No. 2002312654), Japan (No. 4574166) and under application in Europe (EP02737666.4). In addition, RK has also acted as a consultant for Cellestis Inc. for the development of QuantiFERON-CMV assay. Cellestis had no role in study design, data collection and analysis, decision to publish or preparation of the manuscript. The remaining authors declare no conflict of interest.

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Tey, SK., Davenport, M., Hill, G. et al. Post transplant CMV-specific T-cell immune reconstitution in the absence of global T-cell immunity is associated with a high risk of subsequent virus reactivation. Bone Marrow Transplant 50, 315–316 (2015). https://doi.org/10.1038/bmt.2014.265

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