
Contrasting Effects of TGF‐β1 and TNF‐α on the Development of Dendritic Cells from Progenitors in Mouse Bone Marrow
Author(s) -
Yamaguchi Yasunori,
Tsumura Haruhiko,
Miwa Mitsuru,
Inaba Kayo
Publication year - 1997
Publication title -
stem cells
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.159
H-Index - 229
eISSN - 1549-4918
pISSN - 1066-5099
DOI - 10.1002/stem.150144
Subject(s) - biology , cd86 , progenitor cell , bone marrow , immunology , tumor necrosis factor alpha , microbiology and biotechnology , dendritic cell , transforming growth factor beta , population , transforming growth factor , t cell , cancer research , antigen , stem cell , immune system , medicine , environmental health
Dendritic cells (DC) are a distinct population of leukocytes and specialized antigen‐presenting cells for T cell responses. Prior work has shown that GM‐CSF can induce the development of large numbers of DC from proliferating progenitors in mouse bone marrow. We have monitored the effects of potentially enhancing and suppressive cytokines in these cultures. In this system, many immature DC develop from proliferating precursors during the first six days of culture, and between days 6‐8 maturation of typical nonadherent and nonreplicating DC takes place. The maturation is accompanied by a large increase in the expression of major histocompatibilities complex class II (MHC II) and B7‐2/CD86, and in mixed leukocyte reaction stimulating activity. Tumor necrosis factor‐α (TNF‐α), previously shown to be required for development of human DC, was found to enhance the maturation of mouse DC in the last two days of culture. Transforming growth factor‐β1(TGF‐β1), on the other hand, almost totally blocked DC maturation, but it had to be given in the first six days of culture when the DC were actively proliferating. TGF‐β1 did not block the production of immature, MHC II‐positive but B7‐2/CD86‐negative DC. Maturation would take place between days 6‐8 as long as the cultures were depleted of Fc‐receptor‐bearing cells, or if TNF‐α were added. In both instances, maturation was not blocked even when TGF‐β1 remained in the culture. We conclude that the development of DC, in response to GM‐CSF, can be modified by other cytokines. TGF‐β1 is suppressive but only indirectly via Fc‐receptor‐bearing suppressive cells, presumably suppressive macrophages, while TNF‐α enhances the final maturation of DC.