Commitment of juvenile myelo-monocytic (JMML) leukemic cells to spontaneously differentiate into dendritic cells.
Juvenile myelo-monocytic leukemia (JMML) is a severe malignant stem cell disorder of childhood. A proportion of cells from JMML mononuclear cells (MNC) spontaneously differentiate in vitro into dendritic cells (DC). We have studied MNC from 14 JMML patients, and characterized their functional activity as antigen presenting cells (APC). Large cells, differentiated after seven days of culture, expressed high levels of MHC II molecules and Mannose Receptor, variable levels of CD80 and CD86, and low levels of CD1a. Similar to immature DC, cells from JMML had high levels of dextran endocytosis, and were able to elicit proliferation of allogeneic T lymphocytes in mixed leukocyte reaction (MLR). CD40L-matured DC from JMML was associated with relevant increase of CD80, CD86 and CD83, increased APC activity, responded in chemotaxis assays to MIP-3beta and secreted increased amounts of macrophage derived chemokine (MDC). Immature DC and CD40L-matured DC from JMML produced very low amounts of IL-12, whereas the production of IL-10 was higher than normal DC. In line with these findings, they showed defective capacity to polarize naive T cells to differentiate into Th1 effectors. These results indicate that MNC from JMML are committed to spontaneously differentiate into DC with morphological and phenotypical characteristics similar to normal DC. The cytokine profile produced by these APC is likely to suppress and not to elicit a protective immune response.
Longoni
Daniela
D
Clinica Pediatrica-Università degli Studi di Milano-Bicocca, Osp. San Gerardo-Monza, Italy. longonid@libero.it
D'Amico
Giovanna
G
Gaipa
Giuseppe
G
Bernasconi
Sergio
S
Vulcano
Marisa
M
Onnis
Patrizia
P
Niemeyer
Charlotte M
CM
Allavena
Paola
P
Biondi
Andrea
A
D017951:Antigen Presentation / Q000276:immunology; D016022:Case-Control Studies; D002454:Cell Differentiation / Q000502:physiology*; D002648:Child; D002675:Child, Preschool; D003713:Dendritic Cells / Q000166:cytology* / Q000276:immunology; D004705:Endocytosis; D006801:Humans; D007111:Immunity, Cellular; D007223:Infant; D016753:Interleukin-10 / Q000096:biosynthesis / Q000276:immunology; D018664:Interleukin-12 / Q000096:biosynthesis / Q000276:immunology; D015479:Leukemia, Myelomonocytic, Acute / Q000473:pathology*; D008213:Lymphocyte Activation / Q000276:immunology; D007959:Lymphocyte Culture Test, Mixed; D009000:Monocytes / Q000473:pathology
D016753:Interleukin-10; D018664:Interleukin-12