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Bone marrow and thymus expression of interferon-gamma results in severe
B-cell lineage reduction, T-cell lineage alterations, and hematopoietic
progenitor deficiencies
HA Young, DM Klinman, DA Reynolds, KJ Grzegorzewski, A Nii, JM Ward, RT Winkler- Pickett, JR Ortaldo, JJ Kenny and KL Komschlies
Laboratory of Experimental Immunology, National Cancer Institute- Frederick
Cancer Research and Development Center, MD 21702-1201, USA.
Interferon-gamma (IFN-gamma) is an immunoregulatory lymphokine that is
primarily produced by T cells and natural killer cells. It has effects on
T-cell, B-cell, and macrophage differentiation and maturation. We have
developed transgenic mice that express elevated levels of IFN- gamma mRNA
and protein by inserting multiple copies of murine IFN-gamma genomic DNA
containing an Ig lambda-chain enhancer in the first intron. The founder
line carrying eight copies of this transgene has eightfold to 15-fold more
IFN-gamma-producing cells in the bone marrow and spleen than do
nontransgenic littermates. Transgenic mice show a pronounced reduction in
B-lineage cells in the bone marrow, spleen, and lymph nodes. In addition,
single positive (CD4+,CD8- and CD4-,CD8+) thymocyte numbers are increased
twofold, yet the number of splenic T cells is reduced by 50%. There is also
a twofold to threefold decrease in the frequency and total number of
myeloid progenitors in the bone marrow. Granulomatous lesions and residual
degenerating cartilaginous masses are also present in the bones of these
mice. Overall, our data show that the abnormal expression of IFN-gamma in
these transgenic mice results in multiple alterations in the immune system.
These animals provide an important model to examine the role of IFN-gamma
expression on lymphoid and myeloid differentiation and function.
Volume 89,
Issue 2,
pp. 583-595,
01/15/1997
Copyright © 1997 by The American Society of Hematology
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