NZB mice exhibit a primary T cell defect in fetal thymic organ culture.
Document Type
Article
Publication Date
2000
Keywords
Bone-Marrow-Cells, Cell-Differentiation, Histocompatibility-Testing, Leukopoiesis, Lymphopenia, Mice, Mice-Inbred-BALB-C, Mice-Inbred-C57BL, Mice-Inbred-NZB, Organ-Culture, Stem-Cells, SUPPORT-U-S-GOVT-P-H-S, T-Lymphocytes, Thymus-Gland
First Page
1569
Last Page
1575
JAX Source
J Immunol 2000 Feb; 164(3):1569-75.
Grant
AI21256/AI/NIAID, HL60658/HL/NHLBI, AR44173/AR/NIAMS
Abstract
Defects in T cell development have been suggested to be a factor in the development of systemic autoimmunity in NZB mice. However, the suggestion of a primary T cell defect has often been by extrapolation, and few direct observations of T cell precursors in NZB mice have been performed. Moreover, the capacity of NZB bone marrow T cell precursors to colonize the thymus and the ability of the NZB thymic microenvironment to support T lymphopoiesis have not been analyzed. To address this important issue, we employed the fetal thymic organ culture system to examine NZB T cell development. Our data demonstrated that NZB bone marrow cells were less efficient at colonizing fetal thymic lobes than those of control BALB/c or C57BL/6 mice. In addition, NZB bone marrow cells did not differentiate into mature T cells as efficiently as bone marrow cells from BALB/c or C57BL/6 mice. Further analysis revealed that this defect resulted from an intrinsic deficiency in the NZB Lin-Sca-1+c-kit+ bone marrow stem cell pool to differentiate into T cells in fetal thymic organ culture. Taken together, the data document heretofore unappreciated deficiencies in T cell development that may contribute to the development of the autoimmune phenotype in NZB mice.
Recommended Citation
Hashimoto Y,
Dorshkind K,
Montecino RE,
Taguchi N,
Shultz L,
Gershwin ME.
NZB mice exhibit a primary T cell defect in fetal thymic organ culture. J Immunol 2000 Feb; 164(3):1569-75.