Blood Cells - Tissue Functioning and Remodeling in the Circulatory and Ventilatory Systems - page 132

Table 3.31. Regulatory T-cell types (Source: [ 246 ]). Most of FoxP3 + T Reg cells are CD4 + T cells

that express interleukin-2 receptor chain can suppress the activation, proliferation, and effector

functions (e.g., cytokine production) of various populations of immunocytes, such as CD4

α

+ and

CD8 + T c ells, natural killer (NK) and NKT cells, B cells and antigen-presenting cells.

Markers Name Possible origin

CD4 + regulatory T-cell populations
CD4

+ + +

CD25 FoxP3 Natural regulatory T cell Thymus

+ + −

CD4 IL10 FoxP3 Adaptive regulatory T cell, Periphery

Induced regulatory T cell,
T regulatory-1 cell (T R1 )

CD4 + TGF β+ T H 3 cells Periphery

CD8 + regulatory T-cell populations
CD8 + CD25 +

Thymus

CD8 + CD28 − Periphery

CD8 + CD62L + CD122 + ?

+ +

CD8 IL10 Periphery

A third important type of T Reg cell secretes the immunosuppressive cytokine
interleukin-10. It may develop from conventional CD4 T cells subjected to IL10,

or T H1 or T H2 cells [ 245 ]. Other T-cell subpopulations such as natural killer T,
γδ

+

T, and CD8 + T cells can also exert potent suppressor functions in certain

circumstances.
CD4 regulatory T cells develop in the thymus and exhibit a

set of T-cell receptors that are specific for self antigens. Regulatory T cells can also
be generated from effector T cells; these cells then usually do not express forkhead
box protein FoxP3 [ 245 ].
Under certain conditions such as inflammatory environments with high levels of
cytokines (e.g., IL6 and Ifn

+ ,CD25 + , FoxP3 +

) that are normally involved in the polarization toward
effector T cells, FoxP3 expression can be downregulated in FoxP3

γ

T Reg cells.
These cells then lose their suppressor function and manifest some of the functions
of conventional effectors, such as T H1 ,T H2 ,T H17 ,andT FH cells [ 245 ]. In addition,
deletion in T Reg cells of certain transcription factors that are shared between T Reg
and effector cells such as the T H2 -specific factor interferon-regulatory factor IRF4
causes impaired suppression of T H2 responses by T Reg cells [ 245 ]. Such transcrip-
tional submodules rely also on IRF4 for T H17 cells and TBx21 for T H1 [ 241 ].
Therefore, transcription factors of T Reg cells match those of their regulatees. This
matching can help for cohoming.
In any case, regulatory T cells must preserve useful pathogen-specific immune
responses as well as antitumor immunity. Several regulatory T-cell populations exist
(Table 3.31 ). Forkhead box FoxP3

+

T cells can be divided into several
functional populations based on their expression of CD45Ra (human, restricted
form, i.e., synthesized from transcript subtype with exon A), CD45Ro (CD45 lMW :
low-molecular-weight form, the transcript lacking exons A, B, and C), HLADR
(major histocompatibility complex MHC class-2 plasmalemmal [hetero]dimeric re-

+ ,CD4 +