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Integrins
[alpha]4[beta]7 and [alpha]E[beta]7
Are Expressed on Epidermotropic T Cells in Cutaneous T Cell Lymphoma and
Spongiotic Dermatitis |
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Jeffrey
S. Schechner, Richard L. Edelson, Jennifer M. McNiff, Peter W. Heald, and
Jordan S. Pober |
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Departments
of Dermatology (JSS, RLE, JMM, PWH, JSP), Immunobiology (JSP), and Pathology
(JMM, JSP), Yale University School of Medicine, New Haven, Connecticut |
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Integrin [alpha] 4[beta]7
has been associated with tissue-specific homing of malignant and inflammatory
lymphocytes to gastrointestinal mucosa, whereas integrin [alpha]E[beta]7
has been associated with intraepithelial lymphocytes in both the gut and
the skin. This prompted us to examine the expression of [alpha]4[beta]7
on skin-infiltrating lymphocytes in 12 cases of patch/plaque stage cutaneous
T cell lymphoma (CTCL) and in 4 cases of spongiotic dermatitis, which also
display intraepidermal T cell accumulation. [alpha]4[beta]7 was found to
be expressed on 64.8+/- 7.4% of intraepidermal and 39.1 +/- 5.0% of intradermal
T lymphocytes in CTCL. There was a significant positive correlation (r
> = 0.58) between the degree of epidermotropism and the percentage of
intraepidermal T cells expressing [alpha]4[beta]7. Similar findings were
observed in spongiotic dermatitis, indicating that this result is not unique
to malignant T cells. We evaluated staining of T cells in the same specimens
for presence of [alpha]E[beta]7 and observed a strong correlation between
the expression of both [beta]7 integrins in each specimen. Staining with
antibodies directed against the known ligands of [alpha]4[beta]7 was also
performed on skin biopsies from CTCL patients. There was significantly increased
dermal microvascular endothelial expression of vascular cell adhesion molecule-1
in lesional compared with nonlesional skin, and in nonlesional skin compared
with skin of normal control subjects. Dermal and epidermal expression of
the CS-1 domain of fibronectin was present but not increased in lesional
biopsies compared with nonlesional or normal controls, whereas expression
of mucosal addressin cell adhesion molecule-1 was not detectable in any
skin biopsy specimens. In summary, [alpha]4[beta]7, like [alpha]E[beta]7,
is expressed at high levels on epidermotropic T cells and may interact with
endothelial cell vascular cell adhesion molecule-1 as part of stepwise recruitment
of lymphocytes from the blood to the epidermis.(Lab Invest,
79:601-607).
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