Blood Cells - Tissue Functioning and Remodeling in the Circulatory and Ventilatory Systems - page 118

Table 3.21. T cells (Source: [ 223 ]; ID3: Inhibitor of DNA-binding protein-3;

Sox: SRY-related high-mobility group box transcription factor). Signals from T-cell receptors are
strengthened by simultaneous binding of MHC molecules to a specific coreceptor. The coreceptor
corresponds to CD4 and CD8 on CD4

Lineages αβ and γδ

T cells, such as helper and cytotoxic T cells,
respectively. Coreceptors CD4 and CD8 tether class-2 and -1 MHC molecules, respectively. Signals
are delivered by TNFSF2- and TNFSF3-secreting,

+ and CD8 +

αβ , DP thymocytes and received via TNFRSF3

to developing γδ T-cell progenitors to control the competence of γδ T cells rather than their

commitment.

αβ T cells γδ T cells

(conventional) (non-conventional)

Site Predominantly thymus Predominantly epithelia and

and lymph nodes mucosa-associated lymphoid tissues

Upregulation CD4/8

Downregulation CD25 (IL2R α ) CD24

Regulators Sox13

low hi

Receptors IL7R α IL7R α

TCR signal Weak Strong

EGR1 expression Small Great

EGR3 expression Sustained

ID3 Repression Promotion

Environment Notch Notch (initial cell stages)

CXCR4-CXCL12 TNFRSF3

αβ lineages relies on the thymus microenvironment, e.g., TCR and Notch

ligands and lymphotoxin-mediated transconditioning. Extrinsic signals arise from
numerous interactions of T-cell progenitors with stromal cells and other thymocytes.
The lineage divergence occurs at the transition from double-negative DN3a (pre-
selection phase) to DN3b (post-selection phase) [ 223 ]. 112

and γδ

In adults, the population

high low

of DN2 thymocytes can be decomposed into IL7R α and IL7R α subsets that

polarize toward the γδ and αβ T-cell lineages, respectively. Selection between

αβ fate is associated with the upregulation of T-cell surface glycoprotein

CD5 and TNFRSF7 and cell growth. In the

and γδ

α
is downregulated, whereas that of TCR coreceptors CD4 and CD8 is upregulated
to generate double-positive (DP) cells. Double-positive cells undergo TCR

αβ T-cell lineage, expression of IL2R

α gene

rearrangement. The resulting TCR heterodimer then undergoes MHC-mediated

selection to yield mature CD4 or CD8 single-positive (SP) T cells. On the other

αβ

112 The double-negative (DN) thymocyte compartment is subdivided into precursor subsets, such
as DN1a to DN1e, DN2, DN3a and DN3b (a.k.a. DN3e and DN3l, respectively). Transition from
the DN1 to DN2 stage marks the initiation of gene rearrangement at the TCR β ,TCR γ ,andTCR δ
gene loci, a process that is completed at the DN3 stage. At the DN3 stage, preT-cell receptors or
γδ

TCRs impede apoptosis as well as provoke thymocyte proliferation and further differentiation.