T cell development from kit-negative progenitors in the Foxn1Delta/Delta mutant thymus.
Foxn1Delta is a hypomorphic allele of the nude gene that causes arrested thymic epithelial cell differentiation and abnormal thymic architecture lacking cortical and medullary domains. T cells develop in the Foxn1Delta/Delta adult thymus to the double- and single-positive stages, but in the apparent absence of double-negative 3 (DN3) cells; however, DN3 cells are present in the fetal thymus. To investigate the origin of this seemingly contradictory phenotype, we performed an analysis of fetal and adult DN cells in these mutants. Neither adult bone marrow-derived cells nor fetal liver cells from wild-type or Rag1-/- mice were able to differentiate to the DN2 or DN3 stage in the Foxn1Delta/Delta thymus. Our data suggest that thymopoiesis in the Foxn1Delta/Delta adult thymus proceeds from CD117- atypical progenitors, while CD117+ DN1a cells are absent or blocked in their ability to differentiate to the T lineage. Wild-type cells generated by this pathway in the postnatal thymus were exported to the periphery, demonstrating that these atypical cells contributed to the peripheral T cell pool. The Foxn1Delta/Delta adult (but not fetal) thymus also preferentially supports B cell development, specifically of the B-1 type, and this phenotype correlated with reduced Notch ligand expression in the adult stroma.
Xiao
Shiyun
S
Department of Genetics, Coverdell Center, University of Georgia, Athens, GA 30602, USA.
Su
Dong-ming
DM
Manley
Nancy R
NR
D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology; D002454:Cell Differentiation / Q000235:genetics; D051858:Forkhead Transcription Factors / Q000235:genetics / Q000378:metabolism*; D017353:Gene Deletion; D047908:Intracellular Signaling Peptides and Proteins; D007694:Killer Cells, Natural / Q000276:immunology; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D008817:Mice, Mutant Strains; D009154:Mutation; D019009:Proto-Oncogene Proteins c-kit / Q000032:analysis*; D013234:Stem Cells / Q000276:immunology*; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology*; D013950:Thymus Gland / Q000166:cytology / Q000254:growth & development* / Q000276:immunology
D051858:Forkhead Transcription Factors; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; C090140:Whn protein; C064045:delta protein; D019009:Proto-Oncogene Proteins c-kit