Blood Cells - Tissue Functioning and Remodeling in the Circulatory and Ventilatory Systems - page 112

Table 3.19. :

increase; BCL: B-cell lymphoma (leukemia) protein). T-cell progenitors proceed through double-
negative CD4

T-cell specification from thymus-settling progenitors (TSP; Source: [ 215 ]; ↑

stages DN1 to DN4. In thymic niches, Notch-1 activated by Delta-like
ligand DLL4 synthesized by apposed thymic epithelial cells is necessary, but not sufficient for
the T-lineage differentiation program, as alone it does not prevent potential to become a myeloid
cell type. Double-negative-2 cells (DN2) proliferate in response to interleukin-7 also produced
by thymic epithelial cells. Once thymocytes leave the niche, loss of IL7 causes an increase in
BCL11b expression that suppresses alternate lineage development, extinguishes stem cell-like gene
expression, and specifies T-cell fate.

− ,CD8 −

Site Cell type Features

Thymus TSP Migration from bone marrow to thymus

Proliferation as thymocytes

DN1 Stem cell-like

DN2 Multipotent; generation of

dendritic and natural killer cells,
macrophages, and T cells

Thymic niche DN2 Interaction with thymic epithelial cells

that produce IL7 and DLL4
(DLL4-Notch1 juxtacrine interaction)

Thymus DN2 BCL11b expression ↑

DN3 T-cell specification

DN3 cells in the thymus (Table 3.19 ). Differentiation of conventional T cells

from thymic precursors involves a succession of developmental checkpoints that
allow efficient generation of lymphocytes expressing non-autoreactive, self-MHC-
restricted TCRs.
The first

αβ

β checkpoint allows CD4 − ,CD8 − double-negative thymic precursors

that have produced functional TCR β chains to proceed along αβ differentiation

and mature into CD4 double-positive thymocytes (DP). These cells then

undergo selection owing to interaction between

+ ,CD8 +

TCRs and self-MHC-peptide
complexes expressed by epithelial or hematopoietic thymic cells. Thymic TCR
selection permits production of non-harmful, indispensable T cells that can interact
with antigens encountered in the periphery.
The transcription factor B-cell lymphoma BCL11b, or zinc finger protein
ZNF856b, belongs to the earliest regulators for the commitment to the T-cell
lineage [ 216 - 218 ]. Loss of BCL11b generates natural killer-like cells [ 216 ].

αβ

3.10.1.1 ˛ˇ and ı T cells

αβ γδ β

and T cells originate from common thymic precursors. Whereas selection

αβ γδ

engages DN precursors toward the lineage, expression of a functional TCR

γδ

initiates their differentiation into mature T cells. These selections are analogous