Faculty Research 1990 - 1999

Notch activity influences the alphabeta versus gammadelta T cell lineage decision.

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Cell-Differentiation: ph, Cell-Lineage: ph, Chimeric-Proteins: im, CD4-Positive-T-Lymphocytes: cy, ph, CD8-Positive-T-Lymphocytes: cy, ph, Female, Flow-Cytometry, Gene-Dosage, Gene-Rearrangement, Hematopoietic-Stem-Cells: im, Heterozygote, Male, Membrane-Proteins: ge, Mice, Mice-Inbred-C57BL, Mice-Transgenic, Polymerase-Chain-Reaction, Polymorphism-Restriction-Fragment-Length, Receptors-Antigen-T-Cell-alpha-beta: ge, Receptors-Antigen-T-Cell-gamma-delta: ge, Signal-Transduction: im, SUPPORT-NON-U-S-GOVT, SUPPORT-U-S-GOVT-P-H-S, Thymus-Gland: im, cy, Transgenes: im

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Cell 1997 Mar 21;88(6):833-43


The choice between the alphabeta or gammadelta T cell fates is influenced by the production of functional, in-frame rearrangements of the TCR genes, but the mechanism that controls the lineage choice is not known. Here, we show that T cells that are heterozygous for a mutation of the Notch1 gene are more likely to develop as gammadelta T cells than as alphabeta T cells, implying that reduced Notch activity favors the gammadelta T cell fate over the alphabeta T cell fate. A constitutively activated form of Notch produces a reciprocal phenotype and induces thymocytes that have functional gammadeltaTCR gene rearrangements to adopt the alphabeta T cell fate. Our data indicate that Notch acts together with the newly formed T cell antigen receptor to direct the alphabeta versus gammadelta T cell lineage decision.

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