NZB mice exhibit a primary T cell defect in fetal thymic organ culture.
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.
Hashimoto
Y
Y
Division of Rheumatology, University of California, Davis, School of Medicine, Davis, CA 95616, USA.
Dorshkind
K
K
Montecino-Rodriguez
E
E
Taguchi
N
N
Shultz
L
L
Gershwin
M E
ME
D000818:Animals; D001854:Bone Marrow Cells / Q000276:immunology / Q000473:pathology; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology; D006650:Histocompatibility Testing; D019891:Leukopoiesis / Q000276:immunology; D008231:Lymphopenia / Q000235:genetics* / Q000276:immunology* / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008814:Mice, Inbred NZB / Q000235:genetics* / Q000276:immunology*; D009924:Organ Culture Techniques; D013234:Stem Cells / Q000276:immunology / Q000473:pathology; D013601:T-Lymphocytes / Q000276:immunology* / Q000473:pathology; D013950:Thymus Gland / Q000196:embryology* / Q000276:immunology* / Q000473:pathology