Blood Cells - Tissue Functioning and Remodeling in the Circulatory and Ventilatory Systems - page 129

and allergens. Regulatory T cells actually hamper excessive immune reactions
to limit chronic inflammation. In addition, they intervene in allergy, microbial
infection, tumor immunity, and organ transplantation. They also control metabolic
function in adipose tissue. Regulatory T cells represent an actively dividing cell
population [ 238 ].
The control of particular effector functions of conventional T cells (T Conv )
requires distinct programs in T Reg cells. These programs involve the same con-
trolling factors in T Reg lymphocytes and regulated T Conv cells,suchasIRF4in
T H2 lymphocytes and their T Reg controllers [ 239 ]. A given transcriptional program
promotes a particular type of effector T cell (T Eff ) differentiation, to efficiently
restrain the corresponding type of the immune response. In the above-mentioned
example, IRF4 expression endows T Reg cells with a T H2 suppressing function.

T Reg Cell Markers

Regulatory T cells originate primarily in the thymus. Yet, they can be formed from
conventional T cells on exposure to low-dose antigen. T Reg cells are characterized
by a stable expression of the FoxP3 transcription factor. FoxP3 T Reg population

density can be maintained by the differentiation of precursor cells, proliferation of
terminally differentiated cells, and long-life programming. Factor FoxP3 regulates
the bulk of transcriptional program indirectly through a set of target transcriptional
regulators.
FoxP3

+

cells can be generated in the thymus as an alternative lineage during the
selection among CD4

+

thymocytes have a TCR repertoire
that distinguishes them from T Conv cells. Alternatively, mature CD4

+ T-cell lineage. FoxP3 +

+ T cells from

peripheral lymphoid organs can be converted to FoxP3 cells under chronic sub-

optimal stimulation by agonist peptide or during lymphopenia-driven homeostatic
expansion [ 240 ]. In addition, naive CD44

+

+ T Conv cells activated in vitro by IL2 and

TGF express FoxP3 and acquire some features of T Reg cells.

T Reg signature with over- or underexpressed genes distinguishes T Reg from
T Conv cells, at least in their resting states in lymphoid organs (Fig.1 from [ 241 ]).
Molecules involved in T Reg -cell effector function, chemokine receptors, and
transcription factors have expression patterns that define subpopulations. Surface
expressions of

β

α E -integrin (CD103), killer cell lectin-like receptor KLRg1 (or
CLec15a), or CXCR3 vary as well as cell functions [ 240 ]. These subsets of
regulatory T cells (nT Reg ,iT Reg ,andT R1 cells) check the immune system and
impede unrestricted expansion of effector T-cell populations.

Modes of Immunosuppressive Action

CD4 T Eff cells

via a T-cell receptor engagement and cell contact. T-cell receptor-dependent T Reg
activity controls T Eff -cell function. Signaling from TCR leads to the formation
of the immunological synapse within seconds of T-cell activation. Both T Reg

+ ,CD25 + T Reg cells suppress the function of CD4 + and CD8 +