title: Thymic selection can compensate for mutations affecting T cell activation and generate a normal T cell repertoire in mutant mice.
abstract: Thymic selection adjusts the reactivity of the peripheral T cell repertoire to maximize recognition of pathogens and minimize stimulation by innocuous substances and self-antigen. The study of molecules implicated in T cell activation often involves the generation of knockout (-/-) mice. In many instances, knockout animals display revealing phenotypes. But should a lack of phenotype be interpreted as a lack of function? Bcl-xgamma was shown previously to affect T cell activation in vitro, and here we note that overexpression of this molecule increases cell cycling after T cell receptor ligation by antibody. It was therefore surprising that Bcl-xgamma(-/-), Bcl-xgamma transgenic, and WT T cells displayed similar levels of sensitivity to antigen according to ex vivo stimulation. Bcl-xgamma could be demonstrated to influence competitiveness and selection of thymocytes in a manner that counteracted the effects of Bcl-xgamma mutation on T cell activation. These findings suggest that thymic selection can overcome genetic defects in T cell activation to generate a T cell repertoire of normal reactivity.
authors.affiliation: Department of Cancer Immunology and AIDS, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Stephan
authors.initials: S
authors.lastname: Kissler
authors.forename: Linrong
authors.initials: L
authors.lastname: Lu
authors.forename: Harvey
authors.initials: H
authors.lastname: Cantor
mesh_terms: D000818:Animals; D018106:CD28 Antigens / Q000235:genetics; D018956:CD5 Antigens / Q000378:metabolism; D002453:Cell Cycle; D004268:DNA-Binding Proteins / Q000172:deficiency / Q000235:genetics; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000235:genetics / Q000276:immunology / Q000473:pathology; D006023:Glycoproteins / Q000276:immunology; D007108:Immune Tolerance / Q000235:genetics; D066298:In Vitro Techniques; D008213:Lymphocyte Activation / Q000235:genetics*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D063308:Myelin-Oligodendrocyte Glycoprotein; D010446:Peptide Fragments / Q000276:immunology; D010641:Phenotype; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000172:deficiency / Q000235:genetics; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology*; D051020:bcl-X Protein
chemical_list: C494812:Bcl2l1 protein, mouse; D018106:CD28 Antigens; D018956:CD5 Antigens; D004268:DNA-Binding Proteins; D006023:Glycoproteins; D063308:Myelin-Oligodendrocyte Glycoprotein; D010446:Peptide Fragments; D019253:Proto-Oncogene Proteins c-bcl-2; C499308:Rag2 protein, mouse; D011948:Receptors, Antigen, T-Cell; C064655:V(D)J recombination activating protein 2; D051020:bcl-X Protein; C445081:myelin oligodendrocyte glycoprotein (35-55)