INTERFERON-INDUCIBLE PROTEIN-10 AND THE PATHOGENESIS OF CUTANEOUS T-CELL LYMPHOMAS

Human interferon-g inducible protein-10 (IP-10), a small basic protein secreted by interferon (INF)-g stimulated keratinocytes, is chemotact ic for normal CD4-positive lymphocytes and inhibits early normal and l eukemic hemopoietic progenitor proliferation. Cutaneous T-cell lymphom a (CTCL) is an indolent CD4-positive lymphoma characterized by multipl e skin relapses before visceral dissemination. We investigated the rol e of IP-10 in the biology of CTCL by using immunocytochemistry to defi ne IP-10 expression in normal and CTCL skin biopsies. Using purified r ecombinant (r) IP-10, we generated a rabbit antiserum that recognized and neutralized rIP-10 but did not cross-react with any keratinocyte p roteins or any other chemokine. Immunoperoxidase staining of normal ep idermis demonstrated that IP-10 was expressed by basal but not by diff erentiated keratinocytes. The epidermis overlying CTCL lesions was oft en hyperplastic, IP-10 immunostaining was enhanced compared to normal skin, and extended to the suprabasal keratinocytes in 25 of 26 patient s for a frequency of 96%; and 95% confidence interval (CI) of 80% to 1 00%. However, IP-10 was detectable in the dermal or epidermal lymphoid infiltrates in only three of these 26 patients (12%; 95% CI, 2% to 39 %). Skin clinically free of CTCL demonstrated normal IP-10 immunostain ing. In one patient who had matching biopsies performed before and aft er treatment, IP-10 was initially overexpressed before treatment but w as normally expressed when he achieved remission. These results sugges t that IP-10 may play a role in the epidermotropism of CTCL. More work is required to determine whether IP-10 stimulates or inhibits CTCL pr oliferation. A better understanding of the growth controls operating i n CTCL may be used to develop curative therapies for this disorder.