GM-CSF-induced in vivo expansion of splenic dendritic cells and their strong costimulation activity.
Dendritic cells (DC), with their potent antigen-presenting and accessory activities, are involved in the stimulation of naive T cells. To examine the biological functions of DC, we developed a method for generating large numbers of murine splenic DC. First, DC were propagated in vivo by using a granulocyte-macrophage colony-stimulating factor-secreting tumor as a continuous in vivo source of the cytokine. The DC enriched in the spleen, especially in the white pulps, were purified after an overnight culture. We could reproducibly obtain 6 to 10 X 10(6) splenic DC per mouse. These DC were morphologically similar to interdigitating cells, expressed high levels of MHC class II and costimulatory molecules, and were highly allo-stimulatory in mixed lymphocyte reactions. Further analysis on T cell stimulation activity revealed that the DC had strong costimulatory activity on human T cells. Activated B cells, which express both B7-1 and B7-2, had little T cell costimulatory activity under the same assay conditions. A human histiocytic leukemia cell line, U937, that showed only weak costimulatory activity by itself, worked synergistically with DC and further intensified the T cell stimulation by DC. These findings suggest the presence of a T cell costimulation mechanism in DC, which is activated synergistically by monocytes or macrophages, and deserves further study.
Hanada
K
K
Department of Molecular Biotherapy Research, Cancer Institute, Tokyo, Japan.
Tsunoda
R
R
Hamada
H
H
D000818:Animals; D000954:Antigens, Surface / Q000032:analysis; D002450:Cell Communication / Q000502:physiology*; D002452:Cell Count; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000166:cytology* / Q000187:drug effects* / Q000276:immunology; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000378:metabolism* / Q000502:physiology; D006801:Humans; D008213:Lymphocyte Activation; D008264:Macrophages / Q000166:cytology; D008546:Melanoma, Experimental / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D009000:Monocytes / Q000166:cytology; D009368:Neoplasm Transplantation; D013154:Spleen / Q000166:cytology* / Q000187:drug effects* / Q000276:immunology; D013601:T-Lymphocytes / Q000166:cytology
D000954:Antigens, Surface; D016178:Granulocyte-Macrophage Colony-Stimulating Factor