Self-reactivity in thymic double-positive cells commits cells to a CD8 alpha alpha lineage with characteristics of innate immune cells.
Thymocytes displaying self-reactive T cell receptors usually undergo negative selection in the thymus. Here we demonstrate that agonist peptides can promote positive selection of immature double-positive thymocytes into distinct lineages, varying with the agonist concentration and the animal's age. Microarray gene expression analyses showed broad transcriptional alterations in a set of transcripts associated with the innate immune system, as well as silencing of CD8 beta expression. The resulting CD8 alpha alpha T cells showed a rapid effector cytokine response. Hence, T cells displaying self-reactive receptors can have the gene expression profile and phenotypic characteristics of innate immune cells.
Yamagata
Tetsuya
T
Section on Immunology and Immunogenetics, Joslin Diabetes Center; Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, One Joslin Place, Boston, Massachusetts 02215, USA.
Mathis
Diane
D
Benoist
Christophe
C
D000818:Animals; D015551:Autoimmunity / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000502:physiology; D002454:Cell Differentiation / Q000276:immunology / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D015870:Gene Expression / Q000502:physiology; D020869:Gene Expression Profiling; D007113:Immunity, Innate / Q000276:immunology; D008024:Ligands; D051379:Mice; D008810:Mice, Inbred C57BL; D011948:Receptors, Antigen, T-Cell / Q000819:agonists; D013950:Thymus Gland / Q000276:immunology*
D008024:Ligands; D011948:Receptors, Antigen, T-Cell