Tumor Necrosis Factor (TNF) Is a Physiologic Regulator of Hematopoietic Progenitor Cells: Increase of Early Hematopoietic Progenitor Cells in TNF Receptor p55-Deficient Mice In Vivo and Potent Inhibition of Progenitor Cell Proliferation by TNFa In Vitro

Murine bone marrow cells with lineage phenotypes (Lin)Sca-l+c-kit+ and Lin-Sca-l-c-kit+ cells represent primitive hematopoietic stem cells (HSCs) and committed hematopoietic progenitor cells, respectively. The number of Lin-Seal’c-kit’ HSCs in bone marrow was significantly increased in tumor necrosis factor (TNF) receptor p55-deficient (TNFR55-l-l mice compared with the TNF-R55+/+ wild-type mice without a marked change in bone marrow cellularity. In both the methylcellulose culture and a single-cell proliferation assay, mouse TNFa (mTNFa) inhibited in vitro the proliferation of wild-type mouse-derived Lin-Sca-l+c-kit+ cells in response to a combination of multiple growth factors. The same is true for that of Lin-Sca-l-c-kit+ cells stimulated with