Integrins alpha(4)beta(7) and alpha(E)beta(7) are expressed on epidermotropic T cells in cutaneous T cell lymphoma and spongiotic dermatitis

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 lymphocy tes in both the gut and the skin. This prompted us to examine the expressio n 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 p ositive correlation (r = 0.58) between the degree of epidermotropism and th e percentage of intraepidermal T cells expressing alpha(4)beta(7). Similar findings were observed in spongiotic dermatitis, indicating that this resul t is not unique to malignant T cells. We evaluated staining of T cells in t he same specimens for presence of alpha(E)beta(7) and observed a strong cor relation between the expression of both beta(7) integrins in each specimen. Staining with antibodies directed against the known ligands of alpha(4)bet a(7) was also performed on skin biopsies from CTCL patients. There was sign ificantly increased dermal microvascular endothelial expression of vascular cell adhesion molecule-1 in lesional compared with nonlesional skin, and i n nonlesional skin compared with skin of normal control subjects. Dermal an d epidermal expression of the CS-1 domain of fibronectin was present but no t increased in lesional biopsies compared with nonlesional or normal contro ls, whereas expression of mucosal addressin cell adhesion molecule-1 was no t detectable in any skin biopsy specimens. In summary, alpha(4)beta(7), lik e alpha(E)beta(7), is expressed at high levels on epidermotropic T cells an d may interact with endothelial cell vascular cell adhesion molecule-1 as p art of stepwise recruitment of lymphocytes from the blood to the epidermis.