The molecular signature underlying the thymic migration and maturation of TCRαβ+ CD4+ CD8 thymocytes.
BACKGROUND
After positive selection, the newly generated single positive (SP) thymocytes migrate to the thymic medulla, where they undergo negative selection to eliminate autoreactive T cells and functional maturation to acquire immune competence and egress capability.


RESULTS
To elucidate the genetic program underlying this process, we analyzed changes in gene expression in four subsets of mouse TCRαβ(+)CD4(+)CD8(-) thymocytes (SP1 to SP4) representative of sequential stages in a previously defined differentiation program. A genetic signature of the migration of thymocytes was thus revealed. CCR7 and PlexinD1 are believed to be important for the medullary positioning of SP thymocytes. Intriguingly, their expression remains at low levels in the newly generated thymocytes, suggesting that the cortex-medulla migration may not occur until the SP2 stage. SP2 and SP3 cells gradually up-regulate transcripts involved in T cell functions and the Foxo1-KLF2-S1P(1) axis, but a number of immune function-associated genes are not highly expressed until cells reach the SP4 stage. Consistent with their critical role in thymic emigration, the expression of S1P(1) and CD62L are much enhanced in SP4 cells.


CONCLUSIONS
These results support at the molecular level that single positive thymocytes undergo a differentiation program and further demonstrate that SP4 is the stage at which thymocytes acquire the immunocompetence and the capability of emigration from the thymus.
Department of Immunology, Peking University Health Science Center, Beijing, China.
Fei
F
Teng
Yubin
Y
Zhou
Rong
R
Jin
Yu
Y
Chen
Xiaoyan
X
Pei
Yuanfeng
Y
Liu
Jie
J
Dong
Wei
W
Wang
Xuewen
X
Pang
Xiaoping
X
Qian
Wei-Feng
WF
Chen
Yu
Y
Zhang
Qing
Q
Ge
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology* / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology* / Q000378:metabolism; D002448:Cell Adhesion; D002454:Cell Differentiation / Q000235:genetics* / Q000276:immunology; D002465:Cell Movement / Q000235:genetics* / Q000276:immunology; D002469:Cell Separation; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D007121:Immunocompetence; D007700:Kinetics; D008198:Lymph Nodes / Q000166:cytology; D051379:Mice; D008810:Mice, Inbred C57BL; D010641:Phenotype; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000378:metabolism*; D015203:Reproducibility of Results; D058985:Side-Population Cells / Q000166:cytology / Q000378:metabolism; D016176:T-Lymphocyte Subsets / Q000166:cytology / Q000378:metabolism; D060168:Thymocytes / Q000166:cytology / Q000378:metabolism; D013950:Thymus Gland / Q000166:cytology* / Q000378:metabolism
D016693:Receptors, Antigen, T-Cell, alpha-beta