A possible association between the presence of interleukin-4–secreting cells and a reduction in the risk of acute graft-versus-host disease

Abstract

We monitored cytokine-secreting cells using an enzyme-linked immunospot (ELISPOT) assay in a prospective study to assess the cytokine network after transplantation. Peripheral blood mononuclear cells were collected from 23 patients who received allogeneic stem cell transplantation, from before the preconditioning regimen to 56 days after transplantation. The number of interleukin-4 (IL-4), interferon-gamma (IFN-gamma), and tumor necrosis factor-alpha (TNF-alpha)-secreting cells were measured by ELISPOT assay. For IL-4 and IFN-gamma, in vitro stimulation with phorbol 12-myristate 13-acetate and phytohemagglutinin was performed. The frequency of IL-4-secreting cells was significantly higher in five patients receiving peripheral blood stem cell transplantation (PBSCT) than that in 18 patients who received bone marrow transplantation (BMT). Based on IFN-gamma and TNF-alpha release, there was a trend toward a decrease in the number of cytokine-secreting cells in PBSCT compared with BMT. Furthermore, patients who did not develop acute graft-vs-host disease (GVHD, n=5) showed a significantly higher number of IL-4-secreting cells compared with those who developed acute GVHD (n=18). Both IFN-gamma-secreting cells and TNF-alpha-secreting cells showed a trend to increase in number in patients with acute GVHD. In patients who received reduced-intensity stem cell transplantation (n=7) compared with conventional stem cell transplantation (n=16), there was a large number of cytokine-secreting cells detected by IL-4 and IFN-gamma release. These results are consistent with the hypothesis that IL-4-producing cells inhibit the development of acute GVHD. In addition, the increased percentage of IL-4-secreting cells may be responsible for the unexpected low incidence of acute GVHD in PBSCT, despite the presence of large numbers of mature T cells in the donor infusion.