A role for Numb as mediator of CD8 single positive thymocyte migration

The endocytic adaptor Numb, first described in asymmetric division of neural precursors and widely characterized in other model systems, has been less studied in the immune system. By expressing a dominant negative Numb (dnNb) composed by its PTB domain, we have observed a reduction of the CD8 T cell population in the periphery of the transgenic mice. At the age of 12 weeks, these mice present a significant increase in the absolute numbers of CD8 single positive (SP) thymocytes in the thymus. We have verified that CD69 modulation is not altered in CD8 SP thymocytes of the transgenic mouse. Among the complex array of adhesion molecules that are expressed by thymocytes for migration, we have observed intracellular and surface over-expression of the αEβ7 integrin (CD103) that has a restricted expression on CD8 SP thymocytes. It´s ligand, E-cadherin, is expressed on thymic epithelial cells (TEC); nevertheless, migration towards the medullar region is not affected, showing that Numb function on CD8 SP thymocytes may be restricted to migration. These results point out to a differential migration mechanism between CD4 and CD8 SP thymocytes. Our hypothesis is that the SP CD8+ population is retained at the thymic medulla of mice expressing a dominant negative Numb, and migration to the periphery is prevented, due to increased CD103 expression.

Corticomedullar migration analysis.
TG dnNb CD8 thymocytes mice, medulla accumulation (arrow) at age of 12 weeks.

CD103 Flow Cytometry Analysis.
Integrin CD103 overexpression on secondary organs on TG dnNb CD8 thymocytes.