| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
Department of Microbiology-Immunology, Northwestern University, Feinberg School of Medicine, Chicago, IL 60611
Previous evidence suggested that the hemopoietic-specific nuclear factor Ikaros regulates TCR signaling thresholds in mature T cells. In this study, we test the hypothesis that Ikaros also sets TCR signaling thresholds to regulate selection events and CD4 vs CD8 lineage determination in developing thymocytes. Ikaros null mice were crossed to three lines of TCR-transgenic mice, and positive selection, negative selection, and CD4 vs CD8 lineage decisions were analyzed. Mice expressing a polyclonal repertoire or a MHC class II-restricted TCR transgene exhibited enhanced positive selection toward the CD4 lineage. Moreover, in the absence of Ikaros, CD4 development can occur with decreased thresholds of TCR signaling. In addition, CD4 single-positive thymocytes were detected in MHC class I-restricted TCR-transgenic Ikaros null mice. To assess the role of Ikaros in negative selection, we analyzed deletion of T cells induced by conventional Ag or by endogenous superantigen. Surprisingly, negative selection was impaired in Ikaros null thymocytes despite evidence of high levels of TCR signal and no intrinsic defect in apoptosis ex vivo. To our knowledge, these data identify Ikaros as the first nuclear factor that plays a critical role in regulating negative selection as well as CD4 vs CD8 lineage decisions during positive selection.
Related articles in The JI:
This article has been cited by other articles:
|
|
 |
|
  A. L. Hager-Theodorides, A. L. Furmanski, S. E. Ross, S. V. Outram, N. J. Rowbotham, and T. Crompton The Gli3 Transcription Factor Expressed in the Thymus Stroma Controls Thymocyte Negative Selection Via Hedgehog-Dependent and -Independent Mechanisms J. Immunol., September 1, 2009; 183(5): 3023 - 3032. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Q. Cai, A. Dierich, M. Oulad-Abdelghani, S. Chan, and P. Kastner Helios Deficiency Has Minimal Impact on T Cell Development and Function J. Immunol., August 15, 2009; 183(4): 2303 - 2311. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. A. Urban, W. Brugmann, and S. Winandy Cutting Edge: Ikaros Null Thymocytes Mature into the CD4 Lineage with Reduced TCR Signal: A Study Using CD3{zeta} Immunoreceptor Tyrosine-Based Activation Motif Transgenic Mice J. Immunol., April 1, 2009; 182(7): 3955 - 3959. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Chari and S. Winandy Ikaros Regulates Notch Target Gene Expression in Developing Thymocytes J. Immunol., November 1, 2008; 181(9): 6265 - 6274. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. L. Kathrein, S. Chari, and S. Winandy Ikaros Directly Represses the Notch Target Gene Hes1 in a Leukemia T Cell Line: IMPLICATIONS FOR CD4 REGULATION J. Biol. Chem., April 18, 2008; 283(16): 10476 - 10484. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. C. M. Davalos-Misslitz, T. Worbs, S. Willenzon, G. Bernhardt, and R. Forster Impaired responsiveness to T-cell receptor stimulation and defective negative selection of thymocytes in CCR7-deficient mice Blood, December 15, 2007; 110(13): 4351 - 4359. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Schorpp, M. Bialecki, D. Diekhoff, B. Walderich, J. Odenthal, H.-M. Maischein, A. G. Zapata, Tubingen 2000 Screen Consortium, Freiburg Screening Group, and T. Boehm Conserved Functions of Ikaros in Vertebrate Lymphocyte Development: Genetic Evidence for Distinct Larval and Adult Phases of T Cell Development and Two Lineages of B Cells in Zebrafish J. Immunol., August 15, 2006; 177(4): 2463 - 2476. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
