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Induction of Toll-like receptor 2 and 4 expression on CD4+ and CD8+ T cells in G-CSF-mobilized unrelated peripheral blood stem cell grafts during leukapheresis: impact on patient outcome

Leukemia volume 22, pages 1438–1440 (2008)Cite this article

Prior clinical studies have investigated the impact of several donor-graft characteristics on the outcome of patients after hematopoietic cell transplantation.1, 2, 3, 4, 5 Recently, Yakoub-Agha et al.6 presented a study in Leukemia, demonstrating that a high percentage of CD4+CCR7+ T cells in marrow or peripheral blood stem cell (PBSC) grafts significantly correlated with the incidence of acute graft-versus-host disease (GVHD). A current hypothesis concerning its pathogenesis is that epithelial damage in the gut due to components of conditioning facilitates the translocation of lipopolysaccharide, a cell wall component of Gram-negative bacteria into the blood. There, it can initiate proinflammatory cytokine production and activation of different immune cascades, finally leading to a clinical manifestation of GVHD.7 In fact, Toll-like receptors (TLRs) 2 and 4 have been identified as the most important receptors for lipopolysaccharide.8 While the expression and function of TLRs on monocytes have already been widely studied, their role on T cells is not well understood.9 Recent data showed that TLR4 mutation could protect from GVHD10 and that TLR expression on regulatory T cells abrogates their suppressive properties.11 As donor T cells are supposed to be the major effector cells in GVHD, we sought to explore if there is a relevant expression of TLRs on CD4+ and CD8+ T cells in PBSC grafts and study its impact on the development of GVHD, treatment-related mortality, relapse and overall survival of 63 patients receiving unrelated peripheral blood stem cell transplant (PBSCT).

All patients and their respective unrelated donors were treated within protocols at the University Hospital of Dresden. Patient and donor pairs were matched at least in 9 out of 10 alleles (n=17), whereas a complete match (10 out of 10) was observed in 46 patients. Written informed consent was obtained from each patient and donor and all protocols were approved by the institutional review board of the University Hospital Dresden. Patient and graft characteristics are given in Table 1. All patients received a myeloablative conditioning regimen prior to PBSCT and cyclosporine/methotrexate as GVHD prophylaxis as described recently.5 No anti-thymocyte globulin was used during conditioning. All patients received unmanipulated PBSCs on day 0. Cryopreserved aliquots of the donor grafts were thawed and cell-surface antigens were stained using the following series of monoclonal anti-human antibodies: anti-human CD4-PE, anti-human CD3-PECy5, anti-human CD8-FITC (Beckman Coulter, Paris, France), anti-human CD4-FITC (DakoCytomation, Glostrup, Denmark), antihuman TLR2-PE and antihuman TLR4-PE (eBioscience, San Diego, CA, USA). The following antibodies were used as isotype controls: IgG1-PECy5 (BD Pharmingen, Heidelberg, Germany), IgG1-FITC and IgG1-PE (Beckman Coulter, France).

Table 1 Patient and graft characteristics
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Acknowledgements

We thank V Schwarze, A Maiwald and D Doehler for providing assistance with stem cell grafts and Dr K Hölig and her team for performing apheresis procedure in all donors. We are also very grateful to Dr C Thiede and his laboratory for preparation of DNA samples.

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  1. Medizinische Klinik und Poliklinik I, Universitätsklinikum ‘Carl Gustav Carus’ Dresden, Dresden, Germany

    U Platzbecker, J Stoehlmacher, C Pabst, E Goekkurt, U Oelschlägel, H Schirutschke, K Hölig, C Theuser, U Mogck, G Ehninger & M Bornhäuser

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  1. U Platzbecker
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Correspondence to U Platzbecker.

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Platzbecker, U., Stoehlmacher, J., Pabst, C. et al. Induction of Toll-like receptor 2 and 4 expression on CD4+ and CD8+ T cells in G-CSF-mobilized unrelated peripheral blood stem cell grafts during leukapheresis: impact on patient outcome. Leukemia 22, 1438–1440 (2008). https://doi.org/10.1038/sj.leu.2405075

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