Lymphotoxin-mediated regulation of gammadelta cell differentiation by alphabeta T cell progenitors.
The thymus gives rise to two T cell lineages, alphabeta and gammadelta, that are thought to develop independently of one another. Hence, double positive (DP) thymocytes expressing CD4 and CD8 coreceptors are usually viewed simply as progenitors of CD4+ and CD8+ alphabeta T cells. Instead we report that DP cells regulate the differentiation of early thymocyte progenitors and gammadelta cells, by a mechanism dependent on the transcription factor RORgt, and the lymphotoxin (LT) beta receptor (LTbetaR). This finding provokes a revised view of the thymus, in which lymphoid tissue induction-type processes coordinate the developmental and functional integration of the two T cell lineages.
Silva-Santos
Bruno
B
Peter Gorer Department of Immunobiology, Guy's King's St. Thomas' Medical School, King's College, Guy's Hospital, London SE1 9RT, UK.
Pennington
Daniel J
DJ
Hayday
Adrian C
AC
D000818:Animals; D002454:Cell Differentiation; D019070:Cell Lineage; D015870:Gene Expression; D019672:Genes, T-Cell Receptor; D008024:Ligands; D008213:Lymphocyte Activation; D053259:Lymphotoxin beta Receptor; D008233:Lymphotoxin-alpha / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D008565:Membrane Proteins / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3; D010641:Phenotype; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000096:biosynthesis; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000096:biosynthesis; D018168:Receptors, Retinoic Acid / Q000235:genetics / Q000502:physiology*; D011988:Receptors, Thyroid Hormone / Q000235:genetics / Q000502:physiology*; D018124:Receptors, Tumor Necrosis Factor / Q000235:genetics / Q000502:physiology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D016176:T-Lymphocyte Subsets / Q000166:cytology / Q000276:immunology* / Q000502:physiology*; D013950:Thymus Gland / Q000166:cytology / Q000276:immunology*; D014157:Transcription Factors / Q000096:biosynthesis / Q000235:genetics; D053326:Tumor Necrosis Factor Ligand Superfamily Member 14; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics; D015854:Up-Regulation
D008024:Ligands; C505699:Ltbr protein, mouse; D053259:Lymphotoxin beta Receptor; D008233:Lymphotoxin-alpha; D008565:Membrane Proteins; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3; D016693:Receptors, Antigen, T-Cell, alpha-beta; D016692:Receptors, Antigen, T-Cell, gamma-delta; D018168:Receptors, Retinoic Acid; D011988:Receptors, Thyroid Hormone; D018124:Receptors, Tumor Necrosis Factor; C539901:Rorc protein, mouse; C505915:Tnfsf14 protein, mouse; D014157:Transcription Factors; D053326:Tumor Necrosis Factor Ligand Superfamily Member 14; D014409:Tumor Necrosis Factor-alpha