CYTOKINE LOOPS INVOLVING INTERFERON-GAMMA AND IP-10, A CYTOKINE CHEMOTACTIC FOR CD4(- AN EXPLANATION FOR THE EPIDERMOTROPISM OF CUTANEOUS T-CELL LYMPHOMA() LYMPHOCYTES )

Human interferon-gamma (lFN-gamma)-inducible protein 10 (IP-10), a C-X -C chemokine, is secreted by IFN-gamma-stimulated keratinocytes and is chemotactic for CD4(+) lymphocytes. We therefore investigated its rol e in the epidermotropism of cutaneous T-cell lymphoma (CTCL) that is k nown to express IFN-gamma mRNA in the epidermis and is characterized b y an indolent course with multiple relapses that remain confined to th e skin for many years. By injecting purified recombinant (r) IP-10 we generated a polyclonal rabbit antiserum that specifically recognized a nd neutralized rIP-10. With immunoperoxidase staining, IP-10 expressio n was limited to the basal epidermal keratinocytes of normal skin. In biopsies of CTCL lesions the expression of IP-10 was markedly increase d and it extended to the suprabasal keratinocytes in 17 of 18 patients , but it was detectable only faintly in the dermal or epidermal lympho id infiltrates in 2 of these 18 patients. In 1 patient who had matchin g biopsies performed before and after treatment, IP-10 was overexpress ed before treatment, but was normally expressed in the posttreatment b iopsy that showed resolution of the CTCL. Increased IP-10 expression w as not detected in any of 4 patients with B-cell lymphoma involving th e dermis. On the basis of these findings and a review of the literatur e, we propose that secretion of IFN-gamma by the lymphoid infiltrate i n CTCL induces the epidermal keratinocytes to secrete IP-10 that, in t urn, is chemotactic for CTCL, accounting for its epidermotropism. This model may be used as a basis for future investigations of the pathoge nesis of CTCL. (C) 1995 by The American Society of Hematology.