Trial Information

Expression of Chemokine and Chemokine Receptors in Skin in a Model of Delayed-Type Hypersensitivity

In the skin, T lymphocytes are critical modulators and effectors of acquired defense
responses such as delayed-type hypersensitivity (DTH). T lymphocytes and other leukocytes
are recruited to the challenged site via the interaction of selectins, integrins,
immunoglobulin gene superfamily molecules with their ligands, and cytokines including the
large and growing chemokine group. Endogenous proinflammatory agents such as Tumor Necrosis
Factor (TNF)-alpha and Interleukin-1 (IL-1) modulate lymphocyte recruitment via
up-regulation of endothelial adhesion molecules and chemokines. In vitro evidence suggests
that endothelial cell-derived chemokines may play a crucial role in inducing firm arrest of
leukocytes on endothelial cells prior to transmigration. However, the investigation of the
expression patterns and regulation of chemokines in human skin has been limited. Our goal
is to qualitatively and quantitatively investigate changes in chemokine expression patterns
in human skin using a DTH response to mumps antigen as a model T cell mediated immunological
response. We will study the effects of intradermal injection of mumps antigen on cutaneous
chemokine expression in healthy human volunteers over a five-day period. Skin biopsies of
treated and mock-treated areas will be obtained and processed for state-of-the-art,
real-time quantitative RT-PCR analysis of mRNA for chemokines and related molecules of
interest. Routine and immunohistological analysis of chemokine receptor, chemokines,
cytokines and other cell markers on fixed and frozen tissue will also be performed in an
attempt to correlate chemokine expression patterns with the influx of leukocyte subsets into
skin. Our hypothesis is that the chemokines will be up-regulated, but that the kinetics and
expression patterns of individual chemokines may not be identical, thus possibly accounting
for the differential recruitment of T lymphocytes and other leukocytes during the course of
the DTH response. Chemokine expression as determined by quantitative RT-PCR will be
compared with results obtained semi-quantitatively by immunohistochemical staining. This
study may increase the understanding of the pathogenic mechanisms of inflammatory diseases
that are characterized by the recruitment of T lymphocytes, thus possibly identifying
targets for the treatment of cutaneous inflammatory diseases such as psoriasis.