Skewed differentiation of bone marrow CD34+ cells of tumor bearers from dendritic toward monocytic cells, and the redirection of differentiation toward dendritic cells by 1alpha,25-dihydroxyvitamin D3.
Tumor presence is detrimental to the development of antigen-presenting dendritic cells. Since dendritic cells can arise from CD34+ precursor cells, the present study assessed the capacity of bone marrow CD34+ cells from tumor bearers to develop into dendritic cells when cultured in the absence of either tumor cells or their products. Culturing bone marrow CD34+ cells from mice bearing Lewis lung carcinomas yielded a lower number of dendritic cells than arose from CD34+ cells of normal mice. This reduced yield of dendritic cells was associated with a shift to development of monocytic cells and a reduced antigen presenting capability by the cultures. When the CD34+ cell cultures from tumor bearers were supplemented with the differentiation-inducing hormone 1alpha,25-dihydroxyvitamin D3, there was the restoration of dendritic cell development and antigen presenting ability. These results show that CD34+ cells from tumor bearers remain defective in their development into dendritic cells even when cultured outside the tumor environment, but development of dendritic cells can be restored with 1alpha,25-dihydroxyvitamin D3.
Young
M R
MR
Research Service, Hines Veterans Affairs Hospital, Hines, IL 60141, USA
Wright
M A
MA
Vellody
K
K
Lathers
D M
DM
D000818:Animals; D018952:Antigens, CD34; D018827:Carcinoma, Lewis Lung / Q000276:immunology*; D002454:Cell Differentiation / Q000187:drug effects / Q000276:immunology / Q000502:physiology*; D003713:Dendritic Cells / Q000187:drug effects / Q000502:physiology*; D006412:Hematopoietic Stem Cells / Q000187:drug effects / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D009000:Monocytes / Q000187:drug effects / Q000502:physiology*; D009368:Neoplasm Transplantation; D014807:Vitamin D / Q000494:pharmacology*
D018952:Antigens, CD34; D014807:Vitamin D