Biomedical Engineering Reference
In-Depth Information
to the local skin-draining lymph node (LN). Skin-draining LNs are hubs where
mature DCs carrying antigens can interact with T cells expressing cognate receptors
for those antigens, thus connecting the innate and adaptive immune systems. T
cells that encounter their cognate antigen will undergo clonal expansion, produce
autocrine growth factors, and dif erentiate into ef ector memory (T
EM
) or central
memory (T
CM
) cells. Both unactivated and activated/expanded cell populations
return to the blood via the lymphatics. Naïve and T
CM
cells express L-selectin,
CCR7, and LFA-1, which mediate interaction with PNAd, CCL21, and ICAM-1,
respectively. h ese ligands are expressed by high endothelial venules in peripheral
LNs and promote trai c of these cell populations into LNs throughout the body.
Activation of T cells in skin-draining LNs will not only produce T
EM
cells, but will
'imprint' them with a skin homing phenotype (combination of adhesion molecules
and chemokine receptors), allowing them to trai c to skin. In this way, the
immune response is preferentially targeted back to the site of the inciting infection
or inl ammation. Imprinting of homing phenotypes involves the specialized
microenvironment of tissue LNs, tissue-specii c DCs, and soluble factors (Edele
et al.
2008, Sigmundsdottir and Butcher 2008). Recent reports have highlighted an
interesting role for vitamin D in T cell homing to the skin (Sigmundsdottir
et al.
2007).
Secondary Immune Surveillance
Activation of secondary surveillance occurs in the generic context of injury that
leads to the release of inl ammatory cytokines in the epidermis, increased local
expression of endothelial adhesion molecules and recruitment of skin-homing
cells from the circulation. h e T cells that accumulate at this site will bear multiple
distinct antigenic specii c receptors comprising, in ef ect, a representative sample
of the circulating library of T cells specii c for all antigens previously encountered
in the skin. h us, there is immunological memory not only for antigen, but also
for the anatomical context in which that antigen was encountered. h is is an
elegant evolutionary strategy, ensuring that skin injury is considered infectious
until proven otherwise. A non-specii c stimulus in skin leads to accumulation
of a polyclonal population of skin-homing memory T cells that, in the absence
of appropriately presented antigen, eventually exit the skin via the draining
lymphatics. If the stimulus is accompanied by antigen, then the subset of recruited
T cells with the appropriate specii c receptor will become activated by local DCs to
perform their ef ector functions. While circulating CLA+ T cells can be recruited
rapidly to sites of infection or inl ammation, there is also evidence for constitutive
homing of T cells to skin. E-selectin, CCL17, and ICAM-1 are constitutively
expressed on cutaneous microvessels, providing a molecular basis for steady state
homing of CLA+ cells to the skin. Furthermore, T cells recovered from non-
inl amed skin express high levels of CLA and CCR4 (Chong
et al.
2004, Clark
et al.
2006). In fact, calculations based on histological examination indicate that
