TY - JOUR
T1 - Critical roles for IFN-β in lymphoid development, myelopoiesis, and tumor development
T2 - Links to tumor necrosis factor α
AU - Deonarain, Raj
AU - Verma, Amit
AU - Porter, Andrew C.G.
AU - Gewert, Dirk R.
AU - Platanias, Leonidas C.
AU - Fish, Eleanor N.
PY - 2003/11/11
Y1 - 2003/11/11
N2 - We have generated mice null for IFN-β and report the diverse consequences of IFN-β for both the innate and adaptive arms of immunity. Despite no abnormalities in the proportional balance of CD4 and CD8 T cell populations in the peripheral blood, thymus, and spleen of IFN-β -/- mice, activated lymph node and splenic T lymphocytes exhibit enhanced T cell proliferation and decreased tumor necrosis factor α production, relative to IFN-β+/+ mice. Notably, constitutive and induced expression of tumor necrosis factor α is reduced in the spleen and bone marrow (BM) macrophages, respectively, of IFN-β -/- mice. We also observe an altered splenic architecture in IFN-β-/- mice and a reduction in resident macrophages. We identify a potential defect in B cell maturation in IFN-β-/- mice, associated with a decrease in B220+ve/high/cD43-ve BM-derived cells and a reduction in BP-1, IgM, and CD23 expression. Circulating IgM-, Mac-1-, and Gr-1-positive cells are also substantially decreased in IFN-β-/- mice. The decrease in the numbers of circulating macrophages and granulocytes likely reflects defective maturation of primitive BM hematopoiesis in mice, shown by the reduction of colony-forming units, granulocyte-macrophage. We proceeded to evaluate the in vivo growth of malignant cells in the IFN-β-/- background and give evidence that Lewis lung carcinoma-specific tumor growth is more aggressive in IFN-β-/- mice. Taken altogether, our data suggest that, in addition to the direct growth-inhibitory effects on tumor cells, IFN-β is required during different stages of maturation in the development of the immune system.
AB - We have generated mice null for IFN-β and report the diverse consequences of IFN-β for both the innate and adaptive arms of immunity. Despite no abnormalities in the proportional balance of CD4 and CD8 T cell populations in the peripheral blood, thymus, and spleen of IFN-β -/- mice, activated lymph node and splenic T lymphocytes exhibit enhanced T cell proliferation and decreased tumor necrosis factor α production, relative to IFN-β+/+ mice. Notably, constitutive and induced expression of tumor necrosis factor α is reduced in the spleen and bone marrow (BM) macrophages, respectively, of IFN-β -/- mice. We also observe an altered splenic architecture in IFN-β-/- mice and a reduction in resident macrophages. We identify a potential defect in B cell maturation in IFN-β-/- mice, associated with a decrease in B220+ve/high/cD43-ve BM-derived cells and a reduction in BP-1, IgM, and CD23 expression. Circulating IgM-, Mac-1-, and Gr-1-positive cells are also substantially decreased in IFN-β-/- mice. The decrease in the numbers of circulating macrophages and granulocytes likely reflects defective maturation of primitive BM hematopoiesis in mice, shown by the reduction of colony-forming units, granulocyte-macrophage. We proceeded to evaluate the in vivo growth of malignant cells in the IFN-β-/- background and give evidence that Lewis lung carcinoma-specific tumor growth is more aggressive in IFN-β-/- mice. Taken altogether, our data suggest that, in addition to the direct growth-inhibitory effects on tumor cells, IFN-β is required during different stages of maturation in the development of the immune system.
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U2 - 10.1073/pnas.2230460100
DO - 10.1073/pnas.2230460100
M3 - Article
C2 - 14597717
AN - SCOPUS:0345686775
SN - 0027-8424
VL - 100
SP - 13453
EP - 13458
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
IS - 23
ER -