Clonal heterogeneity of dendritic cells derived from patients with chronicmyeloid leukemia and enhancement of their T-cells stimulatory activity by IFN-alpha

Adoptive immunotherapy in form of donor leukocyte infusions is effective in a significant number of patients with chronic myeloid leukemia (CML) that have relapsed after allogeneic bone marrow transplantation (BMT). However, the therapy is associated with clinically significant side effects such as graft-versus-host disease (GVHD) and bone marrow (BM) hypoplasia that may b e avoided through the administration of T cells with specific antileukemic activity. Dendritic cells (DC) functioning as potent antigen presenting cel ls (APC) may play an important role in the generation of T cells with speci ficity against CML. We examined a subpopulation of CD1a(+)/CD14(-) DC gener ated in vitro from BM of normal subjects and patients with CML using granul ocyte-macrophage colony-stimulating factor (GM-CSF), tumor necrosis factor- alpha (TNF-alpha) and interleukin-4 (IL-4). These DC derived from both the BM of normal subjects and of patients with CML, differentiated and matured in culture in a similar way, However, DC derived from patients with CML, di splayed decreased activity when tested with allogeneic T cells in a mixed l ymphocyte reaction (MLR), Addition of interferon-alpha (IFN-alpha) to DC cu ltures significantly upregulated the expression of major histocompatibility complex (MHC) molecules (class I and class II) and costimulatory molecules (B7.1 and B7.2) on DC from normal donors and CML patients. However, DC gro wn from CML patients required a higher concentration of IFN-alpha, IFN-alph a also significantly improved the capacity of CML DC to stimulate T-lymphoc yte responses. Fluorescence in situ hybridization (FISH) showed that only s ome CD1a(+)/CD14(-) DC derived from BM of patients with CML expressed the b cr/abl fusion gene, Incubation with INF-alpha decreased the proportion of b cr/abl positive DC. (C) 1999 International Society for Experimental Hematol ogy. Published by Elsevier Science Inc.