The association of CD25 expression on donor CD8+ and CD4 + T cells with graft-versus-host disease after donor lymphocyte infusions

Background and Objectives. Graft-versus-host disease (GvHD) remains a major complication of allogeneic stem cell transplantation (SCT) and donor lymphocyte infusions (DLI). CD25-expressing donor T cells may be involved in the prevention or induction of GvHD as these cells comprise both CD4 ⁺CD25⁺ regulatory T (Treg) cells and preactivated CD4 ⁺ or CD8⁺ conventional T cells. Therefore, we evaluated the relationship between CD25-expressing CD4⁺ and CD8⁺ donor T cells and the clinical outcome of DLI. Design and Methods. We retrospectively studied the DLI products of 47 HLA-identical DLI recipients by FACS analyses. As Treg cells are often identified within the CD4 ⁺CD25^hiCD45RB^low subset, we determined the frequencies of CD4⁺ and CD8⁺ T cells with different expression levels of CD25 and CD45RB. Results. The frequencies or infused doses of donor CD4⁺CD25⁺ T cells, regardless of their CD25 and CD45RB expression levels, showed no correlation with the clinical outcome in univariate and multivariate analyses. In contrast, elevated frequencies of donor CD8⁺CD25⁺ T cells showed significant correlations with grade II-IV acute GvHD. Patients with GvHD also appeared to have received higher doses of CD8⁺CD25⁺ cells. Increased frequencies of CD8⁺CD25⁺ cells in the DLI products and the infused-doses of these cells also correlated with complete remissions accompanying GvHD. However, there was no correlation between increased levels of CD8 ⁺CD25⁺ cells with complete remissions achieved in the absence of a clinically apparent acute GvHD. Interpretations and Conclusions. Donor CD8⁺CD25⁺ T cells appear to represent a risk factor for GvHD in the DLI setting. Selective depletion of these cells from DLI products may attenuate GvHD without significantly compromising anti-tumor efficacy.