Breaking the Barrier: CD8+ T cells in Atopic Dermatitis and Psoriasis Vulgaris

Atopic dermatitis (AD) is an inflammatory disease that is characterized by a
dysregulated immune response to exogenous factors causing IgE upregulation and
promotion of eosinophilia. Defects in the epidermal permeability barrier play
an important role in the pathogenesis of AD. AD skin is characterized by a
biphasic infiltration of T cells. In the acute phase of AD, effector T cells
are mainly of the T helper-2 (Th2) phenotype. However, in the chronic phase T
helper-1 (Th1) cells are more predominant. Researchers have paid little
attention so far on the role of CD8+ T cells. Preliminary data show increased
numbers of CD8+ T cells in lesional AD skin compared to healthy controls.
Furthermore, we found that a significant subset of these CD8+ T cells produce
the type-2 cytokine interleukin (IL)-13, which is an important immunomodulatory
cytokine that may have an important effect on epithelial barrier function.
In this research proposal, we will investigate the role of IL-13-producing CD8+
T cells. We will try to find out in what stage(s) of disease IL-13-producing
CD8+ T cells are playing a role, by isolating T cells from the skin and
studying T cell phenotype in both acute and chronic AD using the atopy patch
test (APT) as an in vivo induction model. We will further investigate the role
of IL-13 on epidermal barrier function using human skin equivalents.

Results will be compared with psoriasis vulgaris, another T cell mediated
chronic skin disease. This allows us to determine disease specificity of our
results. However, we also expect that our study will contribute to the
knowledge of the pathogenesis of psoriasis vulgaris.

Investigate the role of CD8+ T cells in AD by:
a. Isolation of T cells from the skin and determination of the percentage and
phenotype of CD8+ T cells in both acute and chronic AD, using the APT as an in
vivo induction model. Comparison with psoriasis vulgaris.
b. Investigate effects of IL-13 on epidermal barrier function using human skin
equivalents

observational study

Patients with AD will have to visit the outpatient department three times.
During their first visit an APT will be applied. During a second visit, 24
hours later, the extent of the induced skin reaction will be determined. Skin
punch biopsies (4 mm diameter) will be taken from the APT site, from (chronic)
lesional and from non-lesional skin (three biopsies in total). To determine
disease severity a physical examination will be done to assess a SCORAD and LSS
(AD disease severity) and a blood sample will be taken (10 mL) to determine
serum thymus and activation regulated chemokine (TARC) levels.
Three days after their first visit (72 hours after application of the APT),
another skin biopsy will be taken from an APT site.
Patients with psoriasis vulgaris (PV) will only visit the outpatient department
once for biopsies of lesional and non-lesional skin. During the same visit a
PASI score (psoriasis severity) will be done and a blood sample will be taken
(10 mL). Healthy non-allergic control subjects will visit the the outpatient
department for three biopsies of normal skin and collection of a blood sample.
Risks of skin biopsies include infection and the formation of a (hypopigmented)
scar. After a biopsy is taken, remaining eczematous lesions induced by the APT
can be treated with a topical corticosteroid.