scholarly journals The Absence of Itk Inhibits Positive Selection Without Changing Lineage Commitment

2002 ◽  
Vol 168 (12) ◽  
pp. 6142-6151 ◽  
Author(s):  
Julie A. Lucas ◽  
Luana O. Atherly ◽  
Leslie J. Berg
2000 ◽  
Vol 165 (5) ◽  
pp. 2444-2450 ◽  
Author(s):  
M. Albert Basson ◽  
Timothy J. Wilson ◽  
Giuseppe A. Legname ◽  
Nitza Sarner ◽  
Peter D. Tomlinson ◽  
...  

2005 ◽  
Vol 201 (1) ◽  
pp. 149-158 ◽  
Author(s):  
Henry Kao ◽  
Paul M. Allen

The CD4 coreceptor works together with the T cell receptor (TCR) to deliver signals to the developing thymocyte, yet its specific contribution to positive selection and CD4 lineage commitment remains unclear. To resolve this, we used N3.L2 TCR transgenic, RAG-, and CD4-deficient mice, which are severely impaired in positive selection, and asked whether altered peptide ligands can replace CD4 function in vivo. Remarkably, in the presence of antagonist ligands that normally deleted CD4+ T cells in wild-type mice, we induced positive selection of functional CD4 lineage T cells in mice deficient in CD4. We show that the kinetic threshold for positive and negative selection was lowered in the absence of CD4, with no evident skewing toward the CD8 lineage with weaker ligands. These results suggest that CD4 is dispensable as long as the affinity threshold for positive selection is sustained, and strongly argue that CD4 does not deliver a unique instructional signal for lineage commitment.


1996 ◽  
Vol 26 (2) ◽  
pp. 461-471 ◽  
Author(s):  
Patricia Benveniste ◽  
Gisele Knowles ◽  
Amos Cohen

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Xuyen T. Dinh ◽  
Dragana Stanley ◽  
Letitia D. Smith ◽  
Morgane Moreau ◽  
Stuart P. Berzins ◽  
...  

AbstractiNKT cells play a critical role in controlling the strength and character of adaptive and innate immune responses. Their unique functional characteristics are induced by a transcriptional program initiated by positive selection mediated by CD1d expressed by CD4+CD8+ (double positive, DP) thymocytes. Here, using a novel Vα14 TCR transgenic strain bearing greatly expanded numbers of CD24hiCD44loNKT cells, we examined transcriptional events in four immature thymic iNKT cell subsets. A transcriptional regulatory network approach identified transcriptional changes in proximal components of the TCR signalling cascade in DP NKT cells. Subsequently, positive and negative selection, and lineage commitment, occurred at the transition from DP NKT to CD4 NKT. Thus, this study introduces previously unrecognised steps in early NKT cell development, and separates the events associated with modulation of the T cell signalling cascade prior to changes associated with positive selection and lineage commitment.


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