International Immunology, Vol. 12, No. 3, 335-342,
March 2000
© 2000 Japanese Society for Immunology
Functional heterogeneity among bone marrow-derived dendritic cells conditioned by Th1- and Th2-biasing cytokines for the generation of allogeneic cytotoxic T lymphocytes
1 Section of Genetic Engineering, Research Center for Genetic Engineering and Cell Transplantation, Tokai University School of Medicine, Isehara 259-1193, Kanagawa, Japan
2 Section of Bacterial Infection, Institute of Immunological Science, Hokkaido University, Sapporo 060-0815, Hokkaido, Japan
3 Department of Practical Sciences, Showa Women's University, Setagaya 154-8533, Tokyo, Japan
Correspondence to: T. Nishimura, Section of Bacterial Infection, Institute of Immunological Science, Hokkaido University, Sapporo 060-0815, Hokkaido, Japan
Three distinct bone marrow (BM)-derived dendritic cells (BMDC) were expanded from BALB/c BM cells by culture with (i) granulocyte macrophage colony stimulating factor (GM-CSF) plus IL-3, (ii) GM-CSF, IL-3 plus Th1-biasing cytokines (IL-12 and IFN-
) or (iii) GM-CSF, IL-3 plus Th2-biasing cytokines (IL-4). All of these cells expressed the DC-specific marker CD11c, and were designated as BMDC0, BMDC1 and BMDC2 cells respectively. BMDC1 cells exhibited superior T cell-stimulating activity in allogeneic mixed lymphocyte culture (MLC), while BMDC2 showed inferior stimulating activity. Specifically, BMDC1, as compared with BMDC2, induced a higher frequency of IFN--producing CD8+ T cells in MLC. Moreover, BMDC1, but not BMDC2, were strong inducers of H-2d-specific cytotoxic T lymphocytes (CTL) in MLC. BMDC0 always showed intermediate stimulatory activity; however, when BMDC0 were cultured with IFN-, they differentiated into BMDC1-like stimulator cells concomitant with the up-regulation of both MHC antigens and co-stimulatory molecules. In contrast, BMDC2 were refractory to differentiation into superior stimulator cells by treatment with IFN-, although this treatment enhanced MHC expression. These findings indicate that Th1- and Th2-biasing cytokines, in addition to their effect on Th cell differentiation, may play a critical role in the functional skewing of DC. These findings have important implications for the development of DC-based immunotherapies.
Keywords: cytokine, cytotoxic T lymphocyte, dendritic cells, immunotherapy, Th1/Th2 balance
Transmitting editor: K. Sugamura
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