Bcl-2 is upregulated at the CD4+ CD8+ stage during positive selection and promotes thymocyte differentiation at several control points.
In vivo thymocyte maturation models were used to investigate the differentiation role of Bcl-2. In alpha/beta T cell receptor (TCR) class II-restricted transgenic mice, Bcl-2 was upregulated at the CD4+ CD8+ stage during positive selection. The lckpr-bcl2 transgene was bred onto MHC classes I-I- and II-I-, MHC-I-, and alpha/beta TCR backgrounds to determine whether Bcl-2 promoted thymocyte maturation in the absence of coreceptor-MHC interaction. Bcl-2 rescued CD8+ thymocytes in class I-I- and alpha/beta TCR in mice; however, they were not exported to the periphery. Bcl-2 had no effect on CD4 lineage maturation in class II-I- mice. No single-positive thymocytes accumulate in MHC-I- mice despite overexpressed Bcl-2. Thus, Bcl-2 enables selection of certain TCRs on class II molecules and their differentiation along the CD8 pathway; however, Bcl-2 did not substitute for positive selection. In RAG-1-I- mice, Bcl-2 promoted differentiation to the CD4+ CD8+ stage. Bcl-2 can promote thymocyte maturation at several control points.
Linette
G P
GP
Howard Hughes Medical Institute, Department of Medicine and Pathology, Washington University School of Medicine, St. Louis, Missouri 63110.
Grusby
M J
MJ
Hedrick
S M
SM
Hansen
T H
TH
Glimcher
L H
LH
Korsmeyer
S J
SJ
D000818:Animals; D015704:CD4 Antigens / Q000378:metabolism*; D016827:CD8 Antigens / Q000378:metabolism*; D002454:Cell Differentiation; D015395:Histocompatibility Antigens Class I / Q000378:metabolism; D000949:Histocompatibility Antigens Class II / Q000378:metabolism; D018398:Homeodomain Proteins; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008954:Models, Biological; D011506:Proteins / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D019253:Proto-Oncogene Proteins c-bcl-2; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000378:metabolism; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism*; D015854:Up-Regulation
D015704:CD4 Antigens; D016827:CD8 Antigens; D015395:Histocompatibility Antigens Class I; D000949:Histocompatibility Antigens Class II; D018398:Homeodomain Proteins; D011506:Proteins; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D016693:Receptors, Antigen, T-Cell, alpha-beta; C064658:RAG-1 protein