Impaired development of T lymphoid precursors from pluripotent hematopoietic stem cells in New Zealand Black mice.
Bone marrow cells from autoimmune-prone New Zealand Black (NZB) mice are less efficient at colonizing fetal thymic lobes than cells from normal strains. This study demonstrates that the reduced capacity of NZB bone marrow cells to repopulate the thymus does not result from their inability to migrate to or enter the thymus. Rather, the T lymphopoietic defect of NZB mice is due to an impaired ability of pluripotent hematopoietic stem cells (PHSCs) to generate more committed lymphoid progeny, which could include common lymphoid precursors and/or other T cell-committed progenitors. Although PHSCs from NZB mice were not as efficient at thymic repopulation as comparable numbers of PHSCs from control strains, the ability of common lymphoid precursors from NZB mice to repopulate the thymus was not defective. Similarly, more differentiated NZB T cell precursors included in the intrathymic pool of CD4(-)CD8(-) cells also exhibited normal T lymphopoietic potential. Taken together, the results identify an unappreciated defect in NZB mice and provide further evidence that generation of lymphoid progeny from the PHSCs is a regulated event.
Hashimoto
Yoshiko
Y
Department of Pathology and Laboratory Medicine, Jonsson Comprehensive Cancer Center, University of California School of Medicine, 10833 Le Conte Avenue, Los Angeles, CA 90095, USA.
Montecino-Rodriguez
Encarnacion
E
Gershwin
M Eric
ME
Dorshkind
Kenneth
K
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002454:Cell Differentiation; D002478:Cells, Cultured; D002633:Chemotaxis; D005434:Flow Cytometry; D006412:Hematopoietic Stem Cells / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008814:Mice, Inbred NZB; D013601:T-Lymphocytes / Q000276:immunology*; D013950:Thymus Gland / Q000033:anatomy & histology / Q000196:embryology / Q000276:immunology*