Abnormal myelocytic cell development in interleukin-2 (IL-2)-deficient mice: Evidence for the involvement of IL-2 in myelopiesis

Mice lacking interleukin-2 (IL-2) developed a severe hematopoietic disorder characterized by the abnormal development of myeloid cells and neutropenia. Analysis of the bone marrow of IL-2-deficient (IL-2 (-/-)) mice showed that the number of mature polymorphonuclear cells was decreased by 65% to 75%, and granulocyte/macrophage precursor cells were reduced by 50%. Bone marrow cells from IL-2(-/-) mice were unable to sustain myelopoiesis in lethally irradiated mice and in long-term bone marrow cultures (LTBMC). The addition of exogenous IL-2 to LTBMC of IL-2(-/-) cells partially restored hematopoietic progenitor activity. In the bone marrow of wild-type mice, immature (Mac-1(lo)) myeloid cells, including myeloblasts and promyelocytes, constitutively expressed the β-chain of the IL-2R, and the number of Mac- 1(lo)IL-2Rβ⁺ cells was increased by twofold to threshold in IL-2(-/-) mice. During culture in the presence of IL-2 and the absence of stromal cells, Mac- 1(lo)IL-2Rβ⁺ immature myeloid cells proliferated and gave rise to mature granulocytes and macrophages. Collectively, these observations indicate that defective myelopoiesis in IL-2(-/-) mice is at least in part a consequence of their direct dependency on IL-2, and by regulating the growth of immature myeloid cells, IL-2 plays an important role in the homeostatic regulation of myelocytic cell generation.