Cutting Edge: Ikaros Null Thymocytes Mature into the CD4 Lineage with Reduced TCR Signal: A Study Using CD3ζ Immunoreceptor Tyrosine-Based Activation Motif Transgenic Mice
Cutting Edge: Ikaros Null Thymocytes Mature into the CD4 Lineage with Reduced TCR Signal: A Study Using CD3ζ Immunoreceptor Tyrosine-Based Activation Motif Transgenic Mice
Abstract Positive selection is a critical T cell developmental checkpoint that is driven by TCR signals. Enhanced positive selection toward the CD4 lineage occurs in the absence of Ikaros. One explanation for this phenotype is that Ikaros establishes the TCR signaling threshold that must be overcome for positive selection to occur. In the current study, this possibility is explored through the use of CD3ζ ITAM transgenic mice that express a CD3 ζ-chain with zero, one, or three ITAMs and an MHC class II (DO11.10)- or MHC class I (H-Y)-restricted TCR transgene. Using this system, we demonstrate that in the absence of Ikaros, thymocytes are able to mature into the CD4 lineage with reduced TCR signaling potential compared with that required to drive the maturation of wild-type thymocytes. We also demonstrate that maturation into the CD8 lineage is enhanced under conditions of reduced TCR signaling potential in the absence of Ikaros.
- Northwestern University United States
CD4-Positive T-Lymphocytes, CD3 Complex, Reverse Transcriptase Polymerase Chain Reaction, T-Lymphocytes, Amino Acid Motifs, Blotting, Western, Histocompatibility Antigens Class I, Histocompatibility Antigens Class II, Receptors, Antigen, T-Cell, Cell Differentiation, Mice, Transgenic, CD8-Positive T-Lymphocytes, Ikaros Transcription Factor, Mice, Animals, Cell Lineage, Signal Transduction
CD4-Positive T-Lymphocytes, CD3 Complex, Reverse Transcriptase Polymerase Chain Reaction, T-Lymphocytes, Amino Acid Motifs, Blotting, Western, Histocompatibility Antigens Class I, Histocompatibility Antigens Class II, Receptors, Antigen, T-Cell, Cell Differentiation, Mice, Transgenic, CD8-Positive T-Lymphocytes, Ikaros Transcription Factor, Mice, Animals, Cell Lineage, Signal Transduction
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