Abstract: |
Thymic T cell production is characterized by differentiating waves of non-self-renewing, bone marrow-derived progenitors. The factors constraining new progenitor recruitment, intrathymic precursor expansion, and thymus size remain enigmatic, but are believed to be controlled by a feedback loop responding to lymphoid cellularity and competition for stromal niches. In this study, we show that competition for stromal niches does occur, but is solely limited to cells at the early CD4-8- precursor stages of differentiation. The overall size of the organ is determined both by this limitation on early precursor expansion, and by a second, cell-intrinsic limit on expansion of progenitor cells transiting to the CD4+8+ stage. Together with asymmetric use of marrow-derived progenitors to reconstitute the intrathymic pool, these processes facilitate continuous generation of new T cells while maintaining a relatively stable organ size. |
Keywords: |
controlled study; dna-binding proteins; nonhuman; cd8 antigen; t lymphocyte; animal cell; mouse; animals; mice; mice, knockout; animal tissue; bone marrow; animal experiment; cell differentiation; mice, scid; mice, inbred c57bl; luminescent proteins; mice, transgenic; stem cell; thymus; thymus gland; stroma; green fluorescent proteins; interleukin receptor common gamma subunit; genes, reporter; protein-tyrosine kinases; t-lymphocyte subsets; cd4 antigen; bone marrow transplantation; lymphoid tissue; antigens, cd4; organ size; transplantation chimera; receptors, interleukin-7; antigens, cd8; antigens, cd45; janus kinase 3; specific pathogen-free organisms; priority journal; article; animals, congenic; lymphocytes, null; radiation chimera
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