Biomedical Engineering Reference
In-Depth Information
secondary lymphoid organs (Lefrançois 2006). Shedding of L-selectin on CD34
+
stem cells is a prerequisite of their mobilization into the bloodstream. Naïve T
cells lose expression of L-selectin when leaving thymus for further dif erentiation
into ef ector cells in peripheral lymph nodes. L-selectin expressing T cells home
more ei ciently to lymph nodes. Re-expression of L-selectin is observed in central
memory T cells and is shown to prolong their survival.
Besides L-selectin, lymphocytes express four leukocyte-specii c
β
2
-integrins
(
β
2
-integrin, leukocyte function-
associated antigen 1 (LFA-1), is most abundant and widespread in expression.
In common with many other cell types, lymphocytes express
α
L
β
2
,
α
M
β
2
,
α
X
β
2
and
α
D
β
2
), where the
α
L
β
1
-integrins
mediating binding to ECM (
α
1
-
α
6
β
1
), and the two
α
7
-integrins (
α
4
β
7
and
α
E
β
7
).
It has been shown that
-integrins promote T cell interaction with
endothelial cells playing a crucial role for T cell recirculation and recruitment
to inl ammatory sites.
α
L
β
2
- and
α
4
β
1
β
2
facilitates antigen-dependent interaction of T cells
with antigen presenting cells and target cells. h e interface between a T cell and
an antigen presenting cell is characterized by the immunological synapse, where
the outer ring dei ned by
α
L
β
2
-integrin and the integrin-associated protein talin
surrounds clustered TCRs. Localization of integrins to a lipid rat compartment is
essential for integrin-mediated T cell adhesion. Active
α
L
colocalize
with GM1-enriched rat s and control binding and internalization of the proteins
of Rho family GTPase (Rac, Rho and Cdc42) to rat s. More information about
collaboration between integrins and TCR is given below.
Several integrin-specii c interactions mediate lymphocyte trai cking and
retention at specii c anatomical locations. h e migration of T cells to lymph nodes
is regulated by a tight collaboration between integrins and a panel of chemokine
receptors. Chemokine receptor CCR7 ligands CCL19 and CCL21, as well as the
CXCR5 ligand CXCL13, have been identii ed as central conductors of these events.
It begins with adhesive interaction of T cells with endothelial cells in the high
endothelial venules. h is adhesion is L-selectin dependent, which in combination
with
α
L
β
2
and
α
4
β
1
β
2
and CCR7 is required for T cells to ei ciently enter lymph nodes
(Bromley
et al.
2008). Expression of CCR7 and L-selectin regulates formation of B
cell follicles and T cell areas in secondary peripheral organs.
α
L
α
4
β
7
home to skin and intestine through recognition of
the mucosal addressin MAdCAM-1 expressed by high endothelial venules of Peyer's
patches (Lefrançois 2006). Expression
Lymphocytes expressing
E-integrin, which mediates lymphocyte
binding to epithelial cell E-cadehrin, divides regulatory T cells (Treg) into separate
subpopulations. Expression of
α
E is associated with expression of inl ammatory
chemokine receptors and adhesion molecules that allow their migration into
nonlymphoid tissues.
α
E-positive Treg cell subtype is able to suppress a delayed-
type hypersensitivity response mediated by adoptive transferred antigen-specii c
h 1 cells.
α
