TY - JOUR
T1 - Cutting edge
T2 - Ikaros null thymocytes mature into the CD4 lineage with reduced TCR signal: A study using CD3ζ immunoreceptor tyrosine-based activation motif transgenic mice
AU - Urban, Julie A.
AU - Brugmann, William
AU - Winandy, Susan
PY - 2009/4/1
Y1 - 2009/4/1
N2 - 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 CD3ζITAM 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.
AB - 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 CD3ζITAM 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.
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U2 - 10.4049/jimmunol.0802869
DO - 10.4049/jimmunol.0802869
M3 - Article
C2 - 19299690
AN - SCOPUS:64249086918
SN - 0022-1767
VL - 182
SP - 3955
EP - 3959
JO - Journal of Immunology
JF - Journal of Immunology
IS - 7
ER -