Differences in Kinetics of Donor Lymphoid Cells in Response to G-CSF Administration May Affect the Incidence and Severity of Acute GvHD in Respective HLA-identical Sibling Recipients

Granulocyte-colony stimulating factor (G-CSF), in addition to myeloid and stem cells, mobilizes a large number of lymphoid cells. We examined which lymphoid populations were mobilized in 21 consecutive donors of peripheral blood stem cells (PBSC) and whether the differences in mobilization could affect the incidence of acute and chronic GvHD in respective HLA-identical recipients. G-CSF administration induced significant increases of donor B (CD3-CD19+) lymphocytes and slight increases of T (CD3+) and cytotoxic (CD16+CD56+) NK cells. The number of extrathymic cells (CD3+ cells with NK markers, or CD7+) remained unchanged except for an increase of CD3+CD57+CD8+ cells. Donors of patients without subsequent grade II-IV acute GvHD compared to donors of patients who developed significant acute GvHD were found to have in peripheral blood stable numbers of CD3+CD4+ cells producing IL2, with a concomitant increased number of CD3+CD4low+CD25+ T regulatory cells and decreased NK-mediated cytotoxicity, together with a higher number of suppressive extrathymic CD57+CD3+ cells in the blood and G-PBMC grafts. Increasing numbers of activated T and NK cells in the blood were associated with the development of chronic GvHD. We suggest that differences in steady-state levels and kinetics of G-CSF induced mobilization of donor lymphoid cells may in addition to other well-known factors affect the incidence of GvHD in HLA-identical recipients. However, owing to the small number of donor-recipient pairs studied, our results must be verified in a larger group of patients.