Expression of cutaneous lymphocyte-associated antigen on human CD4(+) and CD8(+) Th2 cells.

The cutaneous lymphocyte-associated antigen (CLA) represents the homing receptor involved in selective migration of memory/effector T cells to the skin. Numerous reports demonstrated distinct CLA expression on Th1 cells. However, T cells isolated from skin lesions and CLA(+) T cells circulating in peripheral blood of atopic dermatitis patients expressed high IL-5 and IL-13. Accordingly, we investigated the regulation of CLA on human type 1 and type 2 T cells. CLA was induced on freshly generated Th1 and Tc1 cells only, but not on those of type 2. Anti-CD3 stimulation was sufficient to induce CLA on Th2 cells in the absence of serum in the culture medium. In serum containing medium, IL-4 inhibited CLA and related alpha-fucosyltransferase mRNA expression. IL-12 and/or staphylococcal enterotoxin B (SEB) stimulation up-regulated CLA expression on either Th2 and Tc2 cells. On stimulation with IL-12, CLA was expressed on the surface of bee venom phospholipase A(2)-specific Th1, Th2, Th0 and T regulatory 1 clones, representing non-skin-related antigen-specific T cells. In addition, CLA could be re-induced on T cells that had lost CLA expression upon resting. These results suggest that skin-selective homing is not restricted to functional and phenotypic T cell subsets.

Clinicopathological and prognostic relevance of Rap1-GAP expression in melanocytic tumors.

Rap1-GAP protein has been identified as an inactivator of Rap1 activity, a putative endogenous antagonist of Ras proteins. The Rap1-GA1 locus maps to 1p36.1-35, the region which may harbor a gene for familial melanoma. In the present immunohistochemical study we analyzed the clinicopathological and prognostic relevance of Rap1-GAP expression in 60 benign and 103 malignant melanocytic tumors. Cytoplasmic immunoreactivity was detected in the cells of 27/60 nevi (45%) and 59/103 melanomas (57%). In the latter group the frequency of Rap1-GAP expression increased (P < 0.05) with the thickness of primary tumors and was highest in metastatic lesions. Rap1-GAP protein was detected in 15/19 subsequently recurring primary melanomas (79%) but only in 32/67 tumors (47%) of patients who remained free of disease (P < 0.05) for at least 6 years. Five out of six recurring thin melanomas (< 2 mm) were found to be immunoreactive. Although being no indicator for malignant transformation of melanocytic lesions, Rap1-GAP overexpression may represent a useful marker for identifying thin high-risk melanomas. Cytoplasmic expression of Rap1-GAP has also been observed in the cells of skin appendages and in keratinocytes, particularly in suprabasal layers of the epidermis. Therefore, Rap1-GAP is likely to be associated with cellular growth and/or differentiation. However, the present study did not provide evidence that this gene, despite its chromosomal localization, represents an early melanoma gene.