TY - JOUR
T1 - Hoxa3 and Pax1 transcription factors regulate the ability of fetal thymic epithelial cells to promote thymocyte development
AU - Su, Dong Ming
AU - Manley, Nancy R.
PY - 2000
Y1 - 2000
N2 - Thymocyte maturation into T cells depends on interactions between thymocytes and thymic epithelial cells. In this study, we show that mutations in two transcription factors, Hoxa3 and Pax1, act synergistically to cause defective thymic epithelial cell development, resulting in thymic ectopia and hypoplasia. Hoxa3(+/-)Pax1(-/-) compound mutant mice exhibited more severe thymus defects than Pax1(-/-) single mutants. Fetal liver adoptive transfer experiments revealed that the defect resided in radio-resistant stromal cells and not in hematopoietic cells. Compound mutants have fewer MHC class II+ epithelial cells, and the level of MHC expression detected was lower. Thymic epithelial cells in these mutants have reduced ability to promote thymocyte development, causing a specific block in thymocyte maturation at an early stage that resulted in a dramatic reduction in the number of CD4+8+ thymocytes. This phenotype was accompanied by increased apoptosis of CD4+8+ thymocytes and their immediate precursors, CD44-25-(CD3-4-8-) cells. Our results identify a transcriptional regulatory pathway required for thymic epithelial cell development and define multiple roles for epithelial cell regulation of thymocyte maturation at the CD4-8- to CD4+8+ transition.
AB - Thymocyte maturation into T cells depends on interactions between thymocytes and thymic epithelial cells. In this study, we show that mutations in two transcription factors, Hoxa3 and Pax1, act synergistically to cause defective thymic epithelial cell development, resulting in thymic ectopia and hypoplasia. Hoxa3(+/-)Pax1(-/-) compound mutant mice exhibited more severe thymus defects than Pax1(-/-) single mutants. Fetal liver adoptive transfer experiments revealed that the defect resided in radio-resistant stromal cells and not in hematopoietic cells. Compound mutants have fewer MHC class II+ epithelial cells, and the level of MHC expression detected was lower. Thymic epithelial cells in these mutants have reduced ability to promote thymocyte development, causing a specific block in thymocyte maturation at an early stage that resulted in a dramatic reduction in the number of CD4+8+ thymocytes. This phenotype was accompanied by increased apoptosis of CD4+8+ thymocytes and their immediate precursors, CD44-25-(CD3-4-8-) cells. Our results identify a transcriptional regulatory pathway required for thymic epithelial cell development and define multiple roles for epithelial cell regulation of thymocyte maturation at the CD4-8- to CD4+8+ transition.
UR - http://www.scopus.com/inward/record.url?scp=0034119902&partnerID=8YFLogxK
U2 - 10.4049/jimmunol.164.11.5753
DO - 10.4049/jimmunol.164.11.5753
M3 - Article
C2 - 10820253
AN - SCOPUS:0034119902
VL - 164
SP - 5753
EP - 5760
JO - Journal of Immunology
JF - Journal of Immunology
SN - 0022-1767
IS - 11
ER -