Regulation of thymus size by competition for stromal niches among early T cell progenitors.
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.
Prockop
Susan E
SE
Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA.
Petrie
Howard T
HT
D000818:Animals; D020296:Animals, Congenic; D016026:Bone Marrow Transplantation; D015704:CD4 Antigens / Q000032:analysis; D016827:CD8 Antigens / Q000032:analysis; D002454:Cell Differentiation; D004268:DNA-Binding Proteins / Q000172:deficiency / Q000235:genetics; D017930:Genes, Reporter; D049452:Green Fluorescent Proteins; D053631:Interleukin Receptor Common gamma Subunit; D053616:Janus Kinase 3; D017493:Leukocyte Common Antigens / Q000032:analysis / Q000235:genetics; D008164:Luminescent Proteins / Q000032:analysis / Q000235:genetics; D008215:Lymphocytes, Null / Q000166:cytology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D016513:Mice, SCID; D008822:Mice, Transgenic; D009929:Organ Size; D011505:Protein-Tyrosine Kinases / Q000172:deficiency / Q000235:genetics; D011828:Radiation Chimera; D020395:Receptors, Interleukin-7 / Q000172:deficiency / Q000235:genetics; D013047:Specific Pathogen-Free Organisms; D016176:T-Lymphocyte Subsets / Q000502:physiology*; D013950:Thymus Gland / Q000166:cytology / Q000254:growth & development*; D018183:Transplantation Chimera
D015704:CD4 Antigens; D016827:CD8 Antigens; D004268:DNA-Binding Proteins; C507942:Il2rg protein, mouse; D053631:Interleukin Receptor Common gamma Subunit; D008164:Luminescent Proteins; C499308:Rag2 protein, mouse; D020395:Receptors, Interleukin-7; C064655:V(D)J recombination activating protein 2; C415350:interleukin-7 receptor, alpha chain; D049452:Green Fluorescent Proteins; D011505:Protein-Tyrosine Kinases; C507935:Jak3 protein, mouse; D053616:Janus Kinase 3; D017493:Leukocyte Common Antigens