Skip to main content
SpringerLink
Log in

Recovery of mucosal-associated invariant T cells after myeloablative chemotherapy and autologous peripheral blood stem cell transplantation

  • Original Article
  • Published:
Clinical and Experimental Medicine Aims and scope Submit manuscript

Abstract

Immune reconstitution after high-dose chemotherapy and stem cell transplantation plays a key role in restoring immunocompetence including defense against infection, immune regulation, and onco-immune surveillance. In this work, we examined the recovery of mucosal-associated invariant T (MAIT) cells, recently discovered innate-like T cells, after various types of myeloablative chemotherapy and autologous peripheral blood stem cell transplantation in 29 patients. We show that MAIT cells are relatively resistant to myeloablative conditioning. The median amount of MAIT cells rises to 43 % around day +30 and is sustained through further measurements on days +60 and +100. Moreover, MAIT cell recovery reaches 100 % of pre-treatment values in 33 % of patients already by day +60. The only factor affecting recovery of MAIT cells is age, younger age being associated with earlier MAIT cell recovery. The pre-treatment quantity of MAIT cells carries a prognostic impact on the early post-transplantation course. Patients with high levels of MAIT cells pre-treatment have significantly lower peak CRP levels (79.45 vs. 150 mg/L) post-treatment, reflecting a clinical trend of less severe infectious complications (less febrile days and less days on intravenous antibiotics). Altogether these data suggest that a high proportion of MAIT cells survive myeloablative chemotherapy and maintain their capacity to fight against infections probably on mucosal surfaces.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

Abbreviations

MAIT:

Mucosal-associated invariant T

TCR:

T cell receptor

MHC:

Major histocompatibility complex

MR1:

MHC-related molecule 1

NK:

Natural killer

PBSCT:

Peripheral blood stem cell transplantation

CRP:

C-reactive protein

G-CSF:

Granulocyte colony-stimulating factor

Tx:

Transplantation

References

  1. Auletta JJ, Lazarus HM. Immune restoration following hematopoietic stem cell transplantation: an evolving target. Bone Marrow Transplant. 2005;35(9):835–57.

    CAS  PubMed  Google Scholar 

  2. Le Bourhis L, Mburu YK, Lantz O. MAIT cells, surveyors of a new class of antigen: development and functions. Curr Opin Immunol. 2013;25(2):174–80.

    PubMed  Google Scholar 

  3. Dusseaux M, Martin E, Serriari N, Péguillet I, Premel V, Louis D, et al. Human MAIT cells are xenobiotic-resistant, tissue-targeted, CD161hi IL-17-secreting T cells. Blood 2011;117(4):1250–9.

    CAS  PubMed  Google Scholar 

  4. Reantragoon R, Corbett AJ, Sakala IG, Gherardin NA, Furness JB, Chen Z, et al. Antigen-loaded MR1 tetramers define T cell receptor heterogeneity in mucosal-associated invariant T cells. J Exp Med. 2013;210(11):2305–20.

    CAS  PubMed  PubMed Central  Google Scholar 

  5. Tilloy F, Treiner E, Park SH, Garcia C, Lemonnier F, de la Salle H, et al. An invariant T cell receptor alpha chain defines a novel TAP-independent major histocompatibility complex class Ib-restricted alpha/beta T cell subpopulation in mammals. J Exp Med. 1999;189(12):1907–21.

    CAS  PubMed  PubMed Central  Google Scholar 

  6. Kjer-Nielsen L, Patel O, Corbett AJ, Le Nours J, Meehan B, Liu L, et al. MR1 presents microbial vitamin B metabolites to MAIT cells. Nature 2012;491(7426):717–23.

    CAS  PubMed  Google Scholar 

  7. Treiner E, Duban L, Bahram S, Radosavljevic M, Wanner V, Tilloy F, et al. Selection of evolutionarily conserved mucosal-associated invariant T cells by MR1. Nature 2003;422(6928):164–9.

    CAS  PubMed  Google Scholar 

  8. Huang S, Martin E, Kim S, Yu L, Soudais C, Fremont DH, et al. MR1 antigen presentation to mucosal-associated invariant T cells was highly conserved in evolution. Proc Natl Acad Sci USA. 2009;106(20):8290–5.

    CAS  PubMed  PubMed Central  Google Scholar 

  9. Le Bourhis L, Martin E, Péguillet I, Guihot A, Froux N, Coré M, et al. Antimicrobial activity of mucosal-associated invariant T cells. Nat Immunol. 2010;11(8):701–8.

    PubMed  Google Scholar 

  10. Grimaldi D, Le Bourhis L, Sauneuf B, Dechartres A, Rousseau C, Ouaaz F, et al. Specific MAIT cell behaviour among innate-like T lymphocytes in critically ill patients with severe infections. Intensive Care Med. 2014;40(2):192–201.

    CAS  PubMed  Google Scholar 

  11. Turtle CJ, Swanson HM, Fujii N, Estey EH, Riddell SR. A distinct subset of self-renewing human memory CD8+ T cells survives cytotoxic chemotherapy. Immunity 2009;31(5):834–44.

    CAS  PubMed  PubMed Central  Google Scholar 

  12. Abrahamsson S V, Angelini DF, Dubinsky AN, Morel E, Oh U, Jones JL, et al. Non-myeloablative autologous haematopoietic stem cell transplantation expands regulatory cells and depletes IL-17 producing mucosal-associated invariant T cells in multiple sclerosis. Brain 2013;136(Pt 9):2888–903.

    PubMed  PubMed Central  Google Scholar 

  13. Mackall CL, Fleisher TA, Brown MR, Andrich MP, Chen CC, Feuerstein IM, et al. Distinctions between CD8+ and CD4+ T-cell regenerative pathways result in prolonged T-cell subset imbalance after intensive chemotherapy. Blood 1997;89(10):3700–7.

    CAS  PubMed  Google Scholar 

  14. Novak J, Dobrovolny J, Novakova L, Kozak T. The decrease in number and change in phenotype of mucosal-associated invariant T cells in the elderly and differences in men and women of reproductive age. Scand J Immunol. 2014;80(4):271–5.

    CAS  PubMed  Google Scholar 

  15. Martin E, Treiner E, Duban L, Guerri L, Laude H, Toly C, et al. Stepwise development of MAIT cells in mouse and human. PLoS Biol. 2009;7(3):e54.

    PubMed  Google Scholar 

  16. Lee O-J, Cho Y-N, Kee S-J, Kim M-J, Jin H-M, Lee S-J, et al. Circulating mucosal-associated invariant T cell levels and their cytokine levels in healthy adults. Exp Gerontol. 2014;49:47–54.

    CAS  PubMed  Google Scholar 

  17. Walker LJ, Tharmalingam H, Klenerman P. The Rise and Fall of MAIT Cells with Age. Scand J Immunol. 2014;80(6):462–3.

    CAS  PubMed  PubMed Central  Google Scholar 

  18. Billerbeck E, Kang Y-H, Walker L, Lockstone H, Grafmueller S, Fleming V, et al. Analysis of CD161 expression on human CD8+ T cells defines a distinct functional subset with tissue-homing properties. Proc Natl Acad Sci USA. 2010;107(7):3006–11.

    PubMed  PubMed Central  Google Scholar 

  19. Offidani M, Corvatta L, Olivieri A, Rupoli S, Frayfer J, Mele A, et al. Infectious complications after autologous peripheral blood progenitor cell transplantation followed by G-CSF. Bone Marrow Transplant. 1999;24(10):1079–87.

    CAS  PubMed  Google Scholar 

Download references

Acknowledgments

We would like to thank Marshall Joseph Andersen from the 3rd Faculty of Medicine, Charles University in Prague, for editing and correcting the English text. Supported by the Research project P 27/2012 awarded by Charles University in Prague, 3rd Faculty of Medicine, Prague, Czech Republic.

Author contribution statement

J.N. contributed to the study conception and design. J.N. and J.D. performed the acquisition of data. J.N., J.D., and J.B. analyzed and interpreted the data. J.N. drafted the manuscript. J.N., J.D., J.B., L.N., and T.K. performed critical revision.

Author information

Authors and Affiliations

  1. Department of Immunology, 3rd Faculty of Medicine, Charles University in Prague, Prague, Czech Republic

    Jan Novak, Jitka Brozova & Lucie Novakova

  2. Department of Internal Medicine and Haematology, 3rd Faculty of Medicine, Charles University in Prague and Faculty Hospital Kralovske Vinohrady, Srobarova 50, 100 34, Prague 10, Czech Republic

    Jan Novak, Jan Dobrovolny & Tomas Kozak

Authors
  1. Jan Novak
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Jan Dobrovolny
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Jitka Brozova
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Lucie Novakova
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Tomas Kozak
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Jan Novak.

Ethics declarations

Compliance with ethical standards

The authors declare that the paper is previously unpublished and is not offered simultaneously elsewhere. All authors have read and approved the content, and all authors also declared that no competing interests exist. The work complies with ethical policies of the journal, and has been conducted under internationally accepted ethical standards after relevant ethical review.

Conflict of interest

The authors declare no conflict of interest.

Electronic supplementary material

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Novak, J., Dobrovolny, J., Brozova, J. et al. Recovery of mucosal-associated invariant T cells after myeloablative chemotherapy and autologous peripheral blood stem cell transplantation. Clin Exp Med 16, 529–537 (2016). https://doi.org/10.1007/s10238-015-0384-z

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10238-015-0384-z

Keywords

Search

Navigation