Abnormal interaction between stromal and hematopoietic cells in tnf deficient mice

TNF is a known regulator of proliferation and differentiation of both primitive and more mature hematopoietic progenitors in culture. However, its effects on hematopoietic stromal cells are not fully understood. We studied the ability of stromal cells from spleen and bone marrow of the TNF deficient mice to maintain hematopoiesis in vivo and in cell culture. We found that the numbers of primitive and more mature hematopoietic precursors were not altered in TNF−/− mice, while the number of stromal precursor cells capable of transferring hematopoietic microenvironment was significantly decreased. Deficiency in stromal cells was further studied in reciprocal bone marrow transfer experiments between the wild type and TNF−/− mice. The number of splenic colonies (CFU-S-derived) was proportional to the number of injected cells when either wild type or TNF−/− donor cells were injected into irradiated recipients of the same genotype. However, this linear relationship was not observed when TNF−/− cells were injected into wild type recipients and visa versa. These results suggest the existence of an important hematopoietic factor (either a population of accessory cells or a signaling molecule) which is regulated by TNF and can be made limiting by TNF inactivation.