INTERFERON-INDUCIBLE PROTEIN-10 AS A POSSIBLE FACTOR IN THE PATHOGENESIS OF CUTANEOUS T-CELL LYMPHOMAS

Human IFN-gamma-inducible protein 10 (IF-10), a C-X-C chemokine secret ed by IFN-gamma-stimulated keratinocytes, is chemotactic for normal CD 4-positive lymphocytes and inhibits the proliferation of early subsets of normal and of leukemic hemopoietic progenitors. Cutaneous T-cell l ymphoma (CTCL) is an indolent lymphoproliferative disorder of CD4-posi tive lymphocytes that remain confined to the skin for many Sears befor e visceral dissemination, Because IFN-gamma mRNA was detected in the e pidermis of CTCL lesions, we decided to investigate the role of IF-10 in the epidermotropism of CTCL by determining its expression in normal skin and in CTCL lesions, Using purified recombinant IF-10 (rIP-10) o r a recombinant fusion protein between IF-10 and the phi 10 protein of phage T7, we generated rabbit antisera that recognized and neutralize d rIP-10. Immunoperoxidase staining of normal epidermis demonstrated t hat IF-10 was expressed by basal keratinocytes but not by the more dif ferentiated cells, In the often hyperplastic epidermis overlying CTCL lesions. IF-10 immunostaining was enhanced compared to normal skin and extended to the suprabasal keratinocytes in 28 of 29 patients for a f requency of 97% and a 95% confidence interval of 82-100%. However, IF- 10 was detectable in the dermal or epidermal lymphoid infiltrates in o nly 3 of 29 patients (10%; 95% confidence interval, 2-29%). Skin clini cally free of CTCL demonstrated normal IP-10 immunostaining. In one pa tient who had matching biopsies performed before and after treatment, IF-10 was overexpressed before treatment but was normally expressed at remission. The in vitro proliferation of primary normal human keratin ocytes was inhibited in a dose-dependent manner by rIP-10. These resul ts suggest that IF-10 plays a role in the epidermotropism of CTCL. Add itional work is needed to determine whether IP-10 stimulates or inhibi ts CTCL proliferation, A better understanding of the growth controls o perating in CTCL may be useful in the development of curative strategi es for this disorder.