Developmental pathway of CD4+CD8- medullary thymocytes during mouse ontogeny and its defect in Aire-/- mice.
The newly generated single-positive (SP) thymocytes undergo further maturation in the thymic medulla before their emigration to the periphery. The present study was undertaken to validate a developmental program we proposed for CD4SP medullary thymocytes and to explore the mechanisms regulating this process. During mouse ontogeny, the emergence of different subsets of CD4SP thymocytes followed a strict temporal order from SP1 to SP4. Parallel to the transition in surface phenotype, a steady increase in function was observed. As further evidence, purified SP1 cells were able to sequentially give rise to SP2, SP3, and SP4 cells in intrathymic adoptive transfer and in culture. Notably, the development of CD4SP cells in the medulla seemed to be critically dependent on a functionally intact medullary epithelial cell compartment because Relb and Aire deficiency were found to cause severe blockage at the transition from SP3 to SP4. Taken together, this work establishes an ontogenetically and functionally relevant maturation program for CD4SP thymocytes. Precise dissection of this program should facilitate further inquiry into the molecular mechanisms governing normal thymocyte development and its disturbance in pathological conditions.
Li
Juan
J
Department of Immunology, Peking University Health Science Center, 38 Xue Yuan Road, Beijing 100083, China.
Li
Yan
Y
Yao
Jin-Yan
JY
Jin
Rong
R
Zhu
Ming-Zhao
MZ
Qian
Xiao-Ping
XP
Zhang
Jun
J
Fu
Yang-Xin
YX
Wu
Li
L
Zhang
Yu
Y
Chen
Wei-Feng
WF
D000818:Animals; D015704:CD4 Antigens / Q000276:immunology*; D016827:CD8 Antigens / Q000276:immunology*; D002454:Cell Differentiation; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D013950:Thymus Gland / Q000166:cytology* / Q000276:immunology; D014157:Transcription Factors / Q000235:genetics / Q000502:physiology*; D000096927:AIRE Protein
D015704:CD4 Antigens; D016827:CD8 Antigens; D014157:Transcription Factors; D000096927:AIRE Protein