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Clinical evidence implicating gamma-delta T cells in EBV control following cord blood transplantation

Bone Marrow Transplantation volume 48, pages 1478–1479 (2013)Cite this article

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Patients who undergo cord-blood transplantation (CBT) offer a unique opportunity to improve our understanding of the impact of viral infection in the early stages of lymphocyte differentiation and function. Viral diseases, including EBV lymphoproliferative disorders, are a major cause of mortality after CBT. Different anti-viral actors are involved in the surveillance of EBV infections.1 While adoptive cellular immune response to EBV infection has been extensively studied, little is known about the role of innate immunity. Some evidence strongly suggests natural killer cell involvement,2 whereas a role for gamma-delta (γδ) T-cells in EBV surveillance has been poorly explored. Gamma-delta T cells are T lymphocytes that exhibit both innate and adaptive features.3 They differ from conventional αβ T cells not only in TCR composition, but also in their development, tissue distribution and physiological functions. The delta chain TCR structure defines two types of the γδ sub-population: a sub-population that expresses the Vδ2 chain mainly present in peripheral blood and another expressing Vδ1, Vδ3 or Vδ5 chains (γδ Vδ2neg). The proliferation of γδ Vδ2neg T cells has been described in various infections, including HIV3 and CMV.4 De Paoli et al.5 have described an expansion of γδ T cells during the acute phase of EBV-induced infectious mononucleosis, suggesting their possible role in the control of EBV infection. Interestingly, after birth, γδ T cells exhibit an earlier activation and differentiation into the memory effector subtype than αβ T cells.6 Moreover, human γδ Vδ2neg T cells exhibit cytotoxic activity in vitro against CMV and EBV lymphocyte cell lines (LCL).4, 7 Consequently, we have hypothesized that these γδ T cells could have also an important role in the surveillance of EBV infection after CBT.

Thus, this CMVneg patient with EBV infection—but no other viral infection—underwent considerable late expansion of γδ T cells from 4% at M3, up to 47% of total T cells at 1 year (vs median 2.6%±2.6) for other CB recipients (n=7)). Such expansion of γδ T cells (up to 40% of total circulating T lymphocytes) has been previously described during CMV infection in transplanted recipient.4 In our patient, most of the γδ T cells were Vδ1pos, differentiated and highly activated (CD57+, CD8+, BTLAlow). Moreover, they were cytotoxic against EBV cell lines. Although the role of Vδ2neg γδ T cells in the surveillance of CMV infection has been clearly demonstrated,9 little is known about their role in the surveillance of EBV infection. Hacker et al.10 have described that EBV-transformed LCLs could stimulate the Vδ1pos subset to proliferate in vitro. Recently, Fujishima et al.7 have demonstrated in a patient who exhibited EBV disease after a BMT, the presence, at 10 years post BMT, of an oligoclonal population of Vδ1pos cells that exhibited in vitro cytotoxicity against autologous and allogenic EBV LCL in a 51Cr-release assay. We demonstrate that Vδ1pos cells from CB expand early after CBT in setting of EBV infection and that, within the first year post CBT, γδ T cells appeared to be differentiated, activated and functional. Collectively, these findings suggest that EBV-infected B cells may cause expansion and activation of Vδ1pos T cells in humans, although natural ligands for Vδ1pos TCR remain to be elucidated. Conversely Vδ1pos T cells may have a TCR repertoire against EBV-infected cells, and may play a role in post-transplant protection against EBV. This implies that enhancement of γδ T-cell replication could be part of the mechanism that enhances the immune response to EBV.

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References

  1. Long HM, Taylor GS, Rickinson AB . Immune defence against EBV and EBV-associated disease. Curr Opin Immunol 2011; 23: 258–264.

    Article  CAS  Google Scholar 

  2. Benoit L, Wang X, Pabst HF, Dutz J, Tan R . Defective NK cell activation in X-linked lymphoproliferative disease. J Immunol 2000; 165: 3549–3553.

    Article  CAS  Google Scholar 

  3. Urban EM, Chapoval AI, Pauza CD . Repertoire development and the control of cytotoxic/effector function in human gammadelta T cells. Clin Dev Immunol 2010; 2010: 732893.

    Article  Google Scholar 

  4. Dechanet J, Merville P, Lim A, Retiere C, Pitard V, Lafarge X et al. Implication of gammadelta T cells in the human immune response to cytomegalovirus. J Clin Invest 1999; 103: 1437–1449.

    Article  CAS  Google Scholar 

  5. De Paoli P, Gennari D, Martelli P, Cavarzerani V, Comoretto R, Santini G . Gamma delta T cell receptor-bearing lymphocytes during Epstein-Barr virus infection. J Infect Dis 1990; 161: 1013–1016.

    Article  CAS  Google Scholar 

  6. De Rosa SC, Andrus JP, Perfetto SP, Mantovani JJ, Herzenberg LA, Roederer M . Ontogeny of gamma delta T cells in humans. J Immunol 2004; 172: 1637–1645.

    Article  CAS  Google Scholar 

  7. Fujishima N, Hirokawa M, Fujishima M, Yamashita J, Saitoh H, Ichikawa Y et al. Skewed T cell receptor repertoire of Vdelta1(+) gammadelta T lymphocytes after human allogeneic haematopoietic stem cell transplantation and the potential role for Epstein-Barr virus-infected B cells in clonal restriction. Clin Exp Immunol 2007; 149: 70–79.

    Article  CAS  Google Scholar 

  8. Deusch K, Luling F, Reich K, Classen M, Wagner H, Pfeffer K . A major fraction of human intraepithelial lymphocytes simultaneously expresses the gamma/delta T cell receptor, the CD8 accessory molecule and preferentially uses the V delta 1 gene segment. Eur J Immunol 1991; 21: 1053–1059.

    Article  CAS  Google Scholar 

  9. Pitard V, Roumanes D, Lafarge X, Couzi L, Garrigue I, Lafon ME et al. Long-term expansion of effector/memory Vdelta2-gammadelta T cells is a specific blood signature of CMV infection. Blood 2008; 112: 1317–1324.

    Article  CAS  Google Scholar 

  10. Hacker G, Kromer S, Falk M, Heeg K, Wagner H, Pfeffer K . V delta 1+ subset of human gamma delta T cells responds to ligands expressed by EBV-infected Burkitt lymphoma cells and transformed B lymphocytes. J Immunol 1992; 149: 3984–3989.

    CAS  PubMed  Google Scholar 

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  1. Immunity and cancer Laboratory, INSERM UMR 1068, Institut Paoli Calmettes, Aix-Marseille Université, Marseille, France

    L Farnault, J Gertner-Dardenne, F Gondois-Rey, I Hirsch & D Olive

  2. Service d’hematologie Pediatrique, CHU La Timone-enfant, Marseille, France

    G Michel & H Chambost

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  1. L Farnault
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  2. J Gertner-Dardenne
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  7. D Olive
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Correspondence to D Olive.

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Farnault, L., Gertner-Dardenne, J., Gondois-Rey, F. et al. Clinical evidence implicating gamma-delta T cells in EBV control following cord blood transplantation. Bone Marrow Transplant 48, 1478–1479 (2013). https://doi.org/10.1038/bmt.2013.75

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