Characterization of the in vivo dynamics of medullary CD4+CD8- thymocyte development.
Our previous studies have defined a differentiation program followed by the newly generated single-positive (SP) thymocytes before their emigration to the periphery. In the present study, we further characterize the development of CD4SP cells in the thymic medulla using mainly intrathymic adoptive transfer assays. By analyzing the differentiation kinetics of the donor cells, which were shown to home correctly to the medullary region following adoptive transfer, we established the precursor-progeny relationship among the four subsets of CD4SP thymocytes (SP1-SP4) and demonstrated that the progression from SP1 to SP4 was unidirectional and largely synchronized. Notably, while the phenotypic maturation from SP1 to SP4 was achieved in 2-3 days, a small fraction of donor cells could be retained in the thymus for a longer period, during which they further matured in function. BrdU incorporation indicated that cell expansion occurred at multiple stages except SP1. Nevertheless, CFSE labeling revealed that only a limited number of cells actually divided during their stay in the medulla. As to the thymic emigration, there was a clear bias toward cells with increasing maturity, but no distinction was found between dividing and nondividing thymocytes. Collectively, these data not only provide solid evidence for a highly ordered differentiation program for CD4SP thymocytes, but they also illustrate several important features associated with the developmental process.
Jin
Rong
R
Department of Immunology, Peking University Health Science Center, 38 Xue Yuan Road, Beijing, China.
Wang
Wei
W
Yao
Jin-Yan
JY
Zhou
Yu-Bin
YB
Qian
Xiao-Ping
XP
Zhang
Jun
J
Zhang
Yu
Y
Chen
Wei-Feng
WF
D019264:Adoptive Transfer; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000637:transplantation*; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology / Q000637:transplantation; D002454:Cell Differentiation / Q000276:immunology*; D002455:Cell Division / Q000276:immunology; D002465:Cell Movement / Q000276:immunology; D016130:Immunophenotyping; D007272:Injections, Intralymphatic; D007694:Killer Cells, Natural / Q000166:cytology / Q000276:immunology / Q000637:transplantation; D051379:Mice; D008810:Mice, Inbred C57BL; D016176:T-Lymphocyte Subsets / Q000166:cytology / Q000276:immunology* / Q000637:transplantation*; D050378:T-Lymphocytes, Regulatory / Q000166:cytology / Q000276:immunology / Q000637:transplantation; D013950:Thymus Gland / Q000166:cytology* / Q000276:immunology* / Q000378:metabolism; D013997:Time Factors