Expression of CD226 antagonizes apoptotic cell death in murine thymocytes.
CD226 is known to be expressed on many types of peripheral lymphoid cells and involved in T cell differentiation, activation, and cytotoxicity. In this study, we report that CD226 is also expressed on mouse thymocytes at varying developmental stages, and its expression is associated with resistance of thymocytes to apoptosis. The levels of CD226 expression appeared to be closely coupled with thymocyte development, in that it was preferentially expressed on CD4(+)CD8(-) and CD4(-)CD8(+) thymocytes at all stages during mouse development, and was markedly increased on the cells in neonatal mice. Of the CD4(+)CD8(+) population, CD226 was predominantly expressed by the cells also positive for CD69, suggesting that CD226 expression may be induced in thymocyte-positive selection. Inhibition of CD226 by short hairpin RNA in a fetal thymus organ culture model led to reduced thymus cellularity, which was associated with enhanced apoptotic cell death. In contrast, CD226-transgenic mice displayed enlarged thymus lobes resulting from increased thymus cellularity. CD226 on thymocytes seemed to play a role in regulating the expression of survivin, as inhibition of CD226 down-regulated survivin, but overexpression of CD226 rescued thymocytes from apoptosis through up-regulation of survivin. In addition, overexpression of CD226 reduced sensitivity of EL-4 thymoma cells to apoptosis by up-regulating the expression of survivin. Taken together, these results indicate that CD226 is an antiapoptotic molecule and may play an important role in murine thymocyte development.
Fang
Liang
L
Department of Immunology, Fourth Military Medical University, Xi'an, People's Republic of China.
Zhang
Xinhai
X
Miao
Jun
J
Zhao
Fang
F
Yang
Kun
K
Zhuang
Ran
R
Bujard
Hermann
H
Wei
Yanzhang
Y
Yang
Angang
A
Chen
Lihua
L
Jin
Boquan
B
D000818:Animals; D000945:Antigens, Differentiation, T-Lymphocyte / Q000096:biosynthesis* / Q000235:genetics / Q000502:physiology; D017209:Apoptosis / Q000235:genetics / Q000276:immunology*; D016923:Cell Death / Q000235:genetics / Q000276:immunology; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology; D002460:Cell Line; D045744:Cell Line, Tumor; D005333:Fetus; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins / Q000096:biosynthesis* / Q000235:genetics / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009924:Organ Culture Techniques; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D013950:Thymus Gland / Q000002:abnormalities / Q000166:cytology* / Q000276:immunology* / Q000378:metabolism; D000098862:T Lineage-Specific Activation Antigen 1
D000945:Antigens, Differentiation, T-Lymphocyte; D000098862:T Lineage-Specific Activation Antigen 1; D051034:Inhibitor of Apoptosis Proteins