Relationship between cytokine-dependent cell cycle progression and MHC class II antigen expression by human CD34+ HLA-DR- bone marrow cells.
Human CD34+ HLA-DR- bone marrow cells constitute a phenotypically homogeneous population of quiescent cells. More than 97% of CD34+ HLA-DR- cells reside in the G0/G1 phase of the cell cycle. The in vitro effects of two cytokines, IL-1 alpha and IL-3, alone or in combination, on the viability, cell cycle status and acquisition of HLA-DR by this cell population were examined. Cell viability was preserved in cultures receiving cytokines, but declined steadily in cultures deprived of exogenous IL. Over a period of 4 days, IL-3 progressively induced the expression of HLA-DR although driving corresponding numbers of cells into S and G2 + M. Although IL-1 alpha induced the expression of HLA-DR, it was not as effective as IL-3 in promoting the exit of these cells from G0/G1. Combinations of IL-1 alpha and IL-3, however, exerted an even greater effect on promoting both HLA-DR expression and entry of cells into active phases of the cell cycle. Simultaneous measurement of HLA-DR expression and cell cycle status in response to IL-1 alpha and IL-3 indicated that the majority of de novo expression of HLA-DR occurred in cells that remained in G0/G1. CD34+ HLA-DR- cells cultured with IL-1 alpha and IL-3 but arrested in G0/G1 by hydroxyurea were still capable of expressing HLA-DR, demonstrating that the acquisition of HLA-DR was independent of the entry of these cells into active phases of the cell cycle. These data indicate that the survival, HLA-DR expression, and cell cycle status of human CD34+ HLA-DR- bone marrow cells are governed by regulatory cytokines such as IL-1 alpha and IL-3. In addition, the entry of these cells into active phases of the cell cycle does not seem to be a prerequisite for the expression of HLA-DR, nor does it seem that the acquisition of HLA-DR by hematopoietic progenitor cells is a marker of cells entering the S phase of the cell cycle.
Srour
E F
EF
Department of Medicine, Indiana University School of Medicine, Indianapolis 46202-5121.
Brandt
J E
JE
Leemhuis
T
T
Ballas
C B
CB
Hoffman
R
R
D015703:Antigens, CD / Q000032:analysis*; D018952:Antigens, CD34; D001853:Bone Marrow / Q000276:immunology; D001854:Bone Marrow Cells; D002453:Cell Cycle / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D006681:HLA-D Antigens / Q000378:metabolism*; D006410:Hematopoiesis; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000276:immunology; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology*; D007377:Interleukin-3 / Q000494:pharmacology*; D013997:Time Factors
D015703:Antigens, CD; D018952:Antigens, CD34; D006681:HLA-D Antigens; D007375:Interleukin-1; D007377:Interleukin-3