Abnormal Myelocytic Cell Development in Interleukin-2 (IL-2)–Deficient Mice: Evidence for the Involvement of IL-2 in Myelopoiesis

Abstract

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-1lo) myeloid cells, including myeloblasts and promyelocytes, constitutively expressed the β-chain of the IL-2R, and the number of Mac-1loIL-2Rβ+ cells was increased by twofold to threefold in IL-2−/− mice. During culture in the presence of IL-2 and the absence of stromal cells, Mac-1loIL-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.

Panax ginseng Modulates Cytokines in Bone Marrow Toxicity and Myelopoiesis: Ginsenoside Rg1 Partially Supports Myelopoiesis

“…In the absence of IL-2, mice develop a profound hematopoietic disorder characterized by defective myelopoiesis and decreased number of mature granulocytes. We obtained conflicting data on IL-2 expression in our experiments [40] . Low concentrations of KG did not enhance IL-2 gene expression, while the highest dose induced a considerable increase in expression.…”

Adenoviral production of interleukin‐2 at the tumor site removes the need for systemic postconditioning in adoptive cell therapy

“…It has been proposed that abnormal myelocytic and lymphoid proliferation outside of the bone marrow constitutes a response to maintain homeostasis similar to the one found in common γ‐chain deficient mice . Noteworthy, most of the marked extramedullary hematopoiesis in the organs is from myeloid progeny confirming the known involvement of IL‐2 in myelopoiesis …”

Interleukin‐15 stimulates macrophages to activate CD4+ T cells: a role in the pathogenesis of rheumatoid arthritis?

“…Myelopoiesis in IL-2-deficient mice is severely disturbed, resulting in an abnormal generation of MF. 35 Interestingly, addition of IL-2 during M-CSF-induced MF generation results in a NK-cell-like phenotype with lytic activity. 36 These findings -in spite of the two shared receptor components argue for an important role of the IL-15Ra chain in mediating the effects during MF differentiation that are described here.…”