title: A model for the origin of TCR-alphabeta+ CD4-CD8- B220+ cells based on high affinity TCR signals.
abstract: The origin of TCR-alphabeta+ CD4-CD8- cells is unclear, yet accumulating evidence suggests that they do not represent merely a default pathway of unselected thymocytes. Rather, they arise by active selection as evidenced by their absence in mice lacking expression of class I MHC. TCR-alphabeta+ CD4-CD8- cells also preferentially accumulate in mice lacking expression of Fas/APO-1/CD95 (lpr) or Fas-ligand (gld), suggesting that this subset might represent a subpopulation destined for apoptosis in normal mice. Findings from mice bearing a self-reactive TCR transgene support this view. In the current study we observe that in normal mice, TCR-alphabeta+ CD4-CD8- thymocytes contain a high proportion of cells undergoing apoptosis. The apoptotic subpopulation is further identified by its expression of B220 and IL2Rbeta and the absence of surface CD2. The CD4-CD8- B220+ phenotype is also enriched in T cells that recognize endogenous retroviral superantigens, and can be induced in TCR transgenic mice using peptide/MHC complexes that bear high affinity, but not low affinity, for TCR. A model is presented whereby the TCR-alphabeta+ CD2- CD4-CD8- B220+ phenotype arises from high intensity TCR signals. This model is broadly applicable to developing thymocytes as well as mature peripheral T cells and may represent the phenotype of self-reactive T cells that are increased in certain autoimmune conditions.
authors.affiliation: Immunobiology Program, Department of Medicine, University of Vermont College of Medicine, Burlington, VT 05405, USA.
authors.forename: P F
authors.initials: PF
authors.lastname: Mixter
authors.forename: J Q
authors.initials: JQ
authors.lastname: Russell
authors.forename: G J
authors.initials: GJ
authors.lastname: Morrissette
authors.forename: C
authors.initials: C
authors.lastname: Charland
authors.forename: D
authors.initials: D
authors.lastname: Aleman-Hoey
authors.forename: R C
authors.initials: RC
authors.lastname: Budd
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D017209:Apoptosis; D018801:CD2 Antigens / Q000302:isolation & purification; D015704:CD4 Antigens / Q000302:isolation & purification*; D016827:CD8 Antigens / Q000302:isolation & purification*; D017493:Leukocyte Common Antigens / Q000302:isolation & purification*; D008285:Major Histocompatibility Complex / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D019463:Mice, Inbred MRL lpr; D008822:Mice, Transgenic; D018448:Models, Immunological; D008969:Molecular Sequence Data; D010047:Ovalbumin / Q000276:immunology; D010446:Peptide Fragments / Q000276:immunology; D010641:Phenotype; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics / Q000302:isolation & purification*; D015375:Receptors, Interleukin-2 / Q000302:isolation & purification; D015398:Signal Transduction; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D013950:Thymus Gland / Q000166:cytology / Q000276:immunology
chemical_list: D018801:CD2 Antigens; D015704:CD4 Antigens; D016827:CD8 Antigens; D010446:Peptide Fragments; D016693:Receptors, Antigen, T-Cell, alpha-beta; D015375:Receptors, Interleukin-2; D010047:Ovalbumin; D017493:Leukocyte Common Antigens