ABNORMAL MYELOCYTIC CELL-DEVELOPMENT IN INTERLEUKIN-2 (IL-2)-DEFICIENT MICE - EVIDENCE FOR THE INVOLVEMENT OF IL-2 IN MYELOPOIESIS

Mice lacking interleukin-2 (IL-2) developed a severe hematopoietic dis order characterized by the abnormal development of myeloid cells and n eutropenia. Analysis of the bone marrow of IL-2-deficient (IL-2(-/-)) mice showed that the number of mature polymorphonuclear cells was decr eased by 65% to 75%, and granulocyte/macrophage precursor cells were r educed by 50%. Bone marrow cells from IL-2(-/-) mice were unable to su stain myelopoiesis in lethally irradiated mice and in long-term bone m arrow 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 beta-chain of the IL-2R, and the number of Mac-1(lo)IL-2R beta(+) cel ls was increased by twofold to threefold in IL-2(-/-) mice. During cul ture in the presence of IL-2 and the absence of stromal cells, Mac-1(l o)IL-2R beta(+) immature myeloid cells proliferated and gave rise to m ature granulocytes and macrophages. Collectively, these observations i ndicate that defective myelopoiesis in IL-2(-/-) mice is at least in p art a consequence of their direct dependency on IL-2, and by regulatin g the growth of immature myeloid cells, IL-2 plays an important role i n the homeostatic regulation of myelocytic cell generation. (C) 1998 b y The American Society of Hematology.