PREDOMINANT EXPRESSION OF CD44 SPLICE VARIANT V10 IN MALIGNANT AND REACTIVE HUMAN SKIN LYMPHOCYTES

The remarkable functional diversity of the cell surface receptor CD44 may be due to expression of multiple variant isoforms generated by alt ernative splicing of variant exons. Functional and correlative data im plicate a role of CD44 variant isoforms in adhesion dependent processe s such as lymphocyte recirculation and tumor progression and metastasi s. We have analyzed 25 primary cutaneous lymphomas and 35 reactive lym phoid cell skin infiltrates or T cell-mediated skin diseases for the e xpression of CD44 variant isoforms. Irrespective of histologic typing, staging, and grading, cutaneous lymphomas as well as nonmalignant ski n-infiltrating CD3(+)CD4(+) and CD8(+) T and CD19(+) B lymphocytes exh ibited a strong expression of CD44v10 and a moderate expression of CD4 4v3 as determined by immunohistochemistry, immunofluorescence microsco py, and mRNA analysis. Expression of v5, v6, v7, and v9-containing CD4 4 variant isoforms was not detected. Furthermore, flow cytometry revea led expression of CD44v10 on a significant proportion of peripheral bl ood lymphocytes from Sezary's syndrome patients and a remarkable coexp ression with cutaneous lymphocyte antigen. These results indicate a di stinct CD44 variant isoform expression pattern associated with skin-ho ming lymphocytes different to lymphatic cells at noncutaneous sites. T his differential expression pattern of CD44 variant isoforms may contr ibute to the development of lymphocyte skin infiltrates and/or the uni que biologic behavior of cutaneous lymphomas.