Expression profiling of a transformed thymocyte cell line undergoing maturation in vitro identifies multiple genes involved in positive selection.
Biochemical and genetic studies of thymocyte maturation would be facilitated by the development of cultured cell lines that reflect stages of positive selection. We have derived a CD4(+)CD8(+)TCR(+) T-lymphoid cell line (M20) from a murine thymic tumor induced by a retrovirus carrying the v-myc oncogene (M-MuLV(myc)). M20 subclones undergo several aspects of positive selection in response to co-culture with a thymic stromal cell line (St3), including down-regulation of CD4 and CD8, and up-regulation of CD5 and TCR. M20 possesses a functional TCR complex, and ligation of this complex produces changes similar to co-culture with St3 stroma. Expression profiling of M20 cells in this system identified 23 genes previously shown to be important in thymocyte maturation, as well as several novel candidate genes. This system provides a new model to elucidate the molecular mechanisms of thymocyte maturation and TCR-mediated cell signaling in double-positive thymocytes.
Division of Hematology/Oncology, Department of Medicine, College of Medicine, Irvine, CA 92697, USA.
S
S
Tiong Ong
Chi
C
Ly
Mark
M
Nguyen
B
B
Kay Brightman
Hung
H
Fan
D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D000945:Antigens, Differentiation, T-Lymphocyte / Q000032:analysis / Q000378:metabolism; D002453:Cell Cycle; D002454:Cell Differentiation; D002460:Cell Line; D002461:Cell Line, Transformed; D002999:Clone Cells; D018920:Coculture Techniques; D020869:Gene Expression Profiling; D016130:Immunophenotyping; D008223:Lymphoma; D051379:Mice; D020411:Oligonucleotide Array Sequence Analysis; D014176:Protein Biosynthesis; D011506:Proteins / Q000235:genetics; D017260:Receptor-CD3 Complex, Antigen, T-Cell / Q000276:immunology; D017154:Stromal Cells / Q000502:physiology; D013601:T-Lymphocytes / Q000145:classification / Q000276:immunology* / Q000378:metabolism; D013950:Thymus Gland / Q000166:cytology / Q000276:immunology*
D000906:Antibodies; D000945:Antigens, Differentiation, T-Lymphocyte; D011506:Proteins; D017260:Receptor-CD3 Complex, Antigen, T-Cell