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Published on: December 26, 2014
Effect of granulocyte colony-stimulating factor mobilization on phenotypical and functional properties of immune
1Etablissement Français du Sang Bourgogne/Franche-Comté, 1, Bd Alexandre Fleming, 25020 Besançon cedex, France.
Insights
Peripheral blood stem cell grafts have significantly higher lymphocyte counts but impaired cytokine production compared to bone marrow grafts. Granulocyte colony-stimulating factor mobilization impacts T-cell activation and cytokine secretion, affecting graft quality.
Area of Science:
- Immunology
- Hematology
- Cell Biology
Background:
- Bone marrow (BM) and peripheral blood stem cell (PBSC) transplantation are common hematologic procedures.
- Mobilization with granulocyte colony-stimulating factor (G-CSF) is used to enhance PBSC collection.
- Understanding the immunophenotypic and functional differences between BM and PBSC grafts is crucial for optimizing transplant outcomes.
Purpose of the Study:
- To compare the phenotypic and functional properties of lymphocytes from BM and G-CSF-mobilized PBSC donors.
- To evaluate the impact of G-CSF mobilization on lymphocyte subsets and their cytokine production capacity.
- To identify quantitative and qualitative differences between BM and PBSC grafts.
Main Methods:
- Randomized study comparing lymphocytes from BM donors (n=27) and PBSC donors (n=23) before and after G-CSF mobilization.
- Immunocytometry analysis of lymphocyte subsets (T, B, NK cells) and expression of activation markers (CD25, CD95, HLA-DR, CD45RA).
- Assessment of cytokine production (IFN-γ, IL-2, TNF-α, IL-4, IL-13) at the protein and mRNA levels.
Main Results:
- G-CSF mobilization increased T and B lymphocyte counts but not NK cells in peripheral blood.
- PBSC grafts had approximately 10-fold higher lymphocyte counts than BM grafts.
- G-CSF reduced T-cell activation and impaired the cytokine production capacity of NK, NK-T, and T cells.
- mRNA levels for both type 1 and type 2 cytokines were significantly lower in PBSC grafts compared to BM grafts.
- No preferential mobilization of suppressive cells or modulation of killer cell receptors was observed.
Conclusions:
- Significant quantitative and qualitative differences exist between BM and PBSC grafts.
- PBSC grafts, while containing more lymphocytes, exhibit an impaired capacity for cytokine production.
- G-CSF mobilization affects lymphocyte function, potentially impacting graft-versus-host responses and immune reconstitution post-transplant.
Abstract:
Some phenotypic and functional properties of lymphocytes from bone marrow or peripheral blood stem cell donors were compared in a randomized study. Lymphocyte subsets were analyzed by immunocytometry in blood harvested from bone marrow donors (n = 27) and from peripheral blood stem cell donors before and after granulocyte colony-stimulating factor mobilization (n = 23) and in bone marrow and peripheral blood stem cell grafts. Granulocyte colony-stimulating factor mobilization increased the blood T and B, but not NK, lymphocyte counts. All lymphocyte counts were approximately 10-fold higher in peripheral blood stem cell grafts than in bone marrow grafts. Analysis of CD25, CD95, HLA-DR, and CD45RA expression shows that T-cell activation level was lower after granulocyte colony-stimulating factor mobilization. Similarly, granulocyte colony-stimulating factor reduced by twofold to threefold the percentage of interferon-gamma, interleukin-2, and tumor necrosis factor-alpha-secreting cells within the NK, NK-T, and T-cell subsets and severely impaired the potential for interferon-gamma production at the single-cell level. mRNA levels of both type 1 (interferon-gamma, interleukin-2) and type 2 (interleukin-4, interleukin-13) cytokines were approximately 10-fold lower in peripheral blood stem cell grafts than in bone marrow grafts. This reduced potential of cytokine production was not associated with a preferential mobilization of so-called "suppressive" cells (CD3+CD4-CD8-, CD3+CD8+CD56+, or CD3+TCRVA24+CD161+), nor with a modulation of killer cell receptors CD161, NKB1, and CD94 expression by NK, NK-T, or T cells. Our data demonstrate in a randomized setting that quantitative as well as qualitative differences exist between a bone marrow and a peripheral blood stem cell graft, whose ability to produce type 1 and type 2 cytokines is impaired.
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