Unequal contribution of Akt isoforms in the double-negative to double-positive thymocyte transition.

Functional domains of Runx1 are differentially required for CD4 repression, TCRbeta expression, and CD4/8 double-negative to CD4/8 double-positive transition in thymocyte development.

Runx1 (AML1) has multiple functions in thymocyte development, including CD4 repression in immature thymocytes, expression of TCRbeta, and efficient beta-selection. To determine the functional domains of Runx1 important for thymocyte development, we cultured Runx1-deficient murine fetal liver (FL) cells on OP9-Delta-like 1 murine stromal cells, which express Delta-like 1 and support thymocyte de...

The essential role of LAT in thymocyte development during transition from the double-positive to single-positive stage.

The linker for activation of T cells (LAT) is an adaptor protein that couples TCR engagement to downstream signaling cascades. LAT is important in early thymocyte development as LAT-deficient mice have a complete block at the double-negative (DN) 3 stage. To study the role of LAT beyond the DN3 stage, we generated mice in which the lat gene could be deleted by the Cre recombinase. Analysis of t...

Akt1 and Akt2 are required for thymocyte survival and differentiation

The -selection checkpoint in T lymphocyte development occurs at the double negative (DN) 3 (CD4 CD8 CD25 c-kit ) stage, when further differentiation requires a signal from the newly rearranged TCR chain. Thymocytes with mutations in key signaling molecules in the phosphatidylinositol 3-kinase–Akt pathway manifest defects in survival, proliferation, and differentiation past the -selection checkp...

Functional Domains of Runx1 Are Differentially Required for CD4 Repression, TCR Expression, and CD4/8 Double-Negative to CD4/8 Double-Positive Transition in Thymocyte Development

Defined αβ T Cell Receptors with Distinct Ligand Specificities Do Not Require Those Ligands to Signal Double Negative Thymocyte Differentiation

During T cell development in the thymus, pre-T cell receptor (TCR) complexes signal CD4(-) CD8(-) (double negative [DN]) thymocytes to differentiate into CD4(+) CD8(+) (double positive [DP]) thymocytes, and they generate such signals without apparent ligand engagements. Although ligand-independent signaling is unusual and might be unique to the pre-TCR, it is possible that other TCR complexes s...