Open Access

ARTICLE

Early pre-engraftment, functional, in vitro responsiveness of T lymphocytes in allotransplanted, acute leukemia patients: proliferation and release of a broad profile of cytokines, possibly predictive of graft-versus-host disease

Knut Liseth¹, Malvin Sjo², Kristin Paulsen³, Øystein Bruserud^2,3, Elisabeth Ersvaer³

1 The Blood Bank, Haukeland University Hospital, Bergen, Norway
2 Department of Medicine, Haukeland University Hospital, Bergen, Norway
3 Institute of Internal Medicine, University of Bergen, Norway

* Corresponding Author: Pr Ø. Bruserud,

European Cytokine Network 2010, 21(1), 40-49. https://doi.org/10.1684/ecn.2009.0181

Accepted 07 November 2009;

Abstract

Previous studies of T cell reconstitution following allogeneic stem cell transplantation have described long-lasting T cell defects, including decreased levels of autocrine proliferating CD4+ T cells. However, T cell functions during the early phase of conditioning-induced, pre-engraftment pancytopenia have not been characterized previously. We used a whole blood assay to investigate T cell proliferation and cytokine release during the period of pre-engraftment cytopenia. The study included 13 acute leukemia patients receiving mye-loablative conditioning followed by transplantation of G-CSF-mobilised peripheral blood stem cells derived from HLA-matched family donors. Maximal proliferation and cytokine release could not be reached by anti-CD3 stimulation alone, but was dependent on the presence of additional costimulation with anti-CD28. Circulat-ing T cells showed a broad cytokine release profile after activation, and the highest levels were detected for IFNγ, GM-CSF and IL-6. Correlation analyses showed that TNFα/IL-4/IL-5/IL-13 in particular were released as a separate cluster, IFNγ and GM-CSF correlated strongly, whereas IL-17 showed a weak correlation to IL-6 only. The capacity of circulating T cells derived during pre-engraftment cytopenia to release high levels of IFNγ, IL-6 and IL-17 in response to in vitro activation with anti-CD3+anti-CD28 showed statistically significant corre-lations with later acute GVHD. We conclude that allotransplanted patients have a functional T cell system even during the pre-engraftment period of severe pancytopenia.

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