title: Interferon-inducible protein 10 as a possible factor in the pathogenesis of cutaneous T-cell lymphomas.
abstract: Human IFN-gamma-inducible protein 10 (IP-10), a C-X-C chemokine secreted by IFN-gamma-stimulated keratinocytes, is chemotactic for normal CD4-positive lymphocytes and inhibits the proliferation of early subsets of normal and of leukemic hemopoietic progenitors. Cutaneous T-cell lymphoma (CTCL) is an indolent lymphoproliferative disorder of CD4-positive lymphocytes that remain confined to the skin for many years before visceral dissemination. Because IFN-gamma mRNA was detected in the epidermis of CTCL lesions, we decided to investigate the role of IP-10 in the epidermotropism of CTCL by determining its expression in normal skin and in CTCL lesions. Using purified recombinant IP-10 (rIP-10) or a recombinant fusion protein between IP-10 and the straight phi10 protein of phage T7, we generated rabbit antisera that recognized and neutralized rIP-10. Immunoperoxidase staining of normal epidermis demonstrated that IP-10 was expressed by basal keratinocytes but not by the more differentiated cells. In the often hyperplastic epidermis overlying CTCL lesions, IP-10 immunostaining was enhanced compared to normal skin and extended to the suprabasal keratinocytes in 28 of 29 patients for a frequency of 97% and a 95% confidence interval of 82-100%. However, IP-10 was detectable in the dermal or epidermal lymphoid infiltrates in only 3 of 29 patients (10%; 95% confidence interval, 2-29%). Skin clinically free of CTCL demonstrated normal IP-10 immunostaining. In one patient who had matching biopsies performed before and after treatment, IP-10 was overexpressed before treatment but was normally expressed at remission. The in vitro proliferation of primary normal human keratinocytes was inhibited in a dose-dependent manner by rIP-10. These results suggest that IP-10 plays a role in the epidermotropism of CTCL. Additional work is needed to determine whether IP-10 stimulates or inhibits CTCL proliferation. A better understanding of the growth controls operating in CTCL may be useful in the development of curative strategies for this disorder.
authors.affiliation: Departments of Hematology, Medical Specialties, and Pathology, University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030, USA.
authors.forename: A H
authors.initials: AH
authors.lastname: Sarris
authors.forename: D
authors.initials: D
authors.lastname: Daliani
authors.forename: R
authors.initials: R
authors.lastname: Ulmer
authors.forename: M
authors.initials: M
authors.lastname: Crow
authors.forename: H E
authors.initials: HE
authors.lastname: Broxmeyer
authors.forename: M
authors.initials: M
authors.lastname: Reiss
authors.forename: N
authors.initials: N
authors.lastname: Karasavvas
authors.forename: A D
authors.initials: AD
authors.lastname: Zelenetz
authors.forename: W
authors.initials: W
authors.lastname: Pugh
authors.forename: F
authors.initials: F
authors.lastname: Cabanillas
authors.forename: A B
authors.initials: AB
authors.lastname: Deisseroth
authors.forename: M
authors.initials: M
authors.lastname: Duvic
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002455:Cell Division; D054357:Chemokine CXCL10; D019743:Chemokines, CXC / Q000096:biosynthesis / Q000502:physiology*; D016207:Cytokines / Q000378:metabolism; D005260:Female; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism*; D015603:Keratinocytes / Q000378:metabolism / Q000473:pathology; D016410:Lymphoma, T-Cell, Cutaneous / Q000209:etiology* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D012878:Skin Neoplasms / Q000209:etiology* / Q000473:pathology
chemical_list: D054357:Chemokine CXCL10; D019743:Chemokines, CXC; D016207:Cytokines; D007371:Interferon-gamma