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 chemotactic for normal CD4-positive lymphocytes and inhibits early normal and leukemic hemopoietic progenitor proliferation. Cutaneous T-cell lymphoma (CTCL) is an indolent CD4-positive lymphoma characterized by multiple skin relapses before visceral dissemination. We investigated the role of IP-10 in the biology of CTCL by using immunocytochemistry to define IP-10 expression in normal and CTCL skin biopsies. Using purified recombinant (r) IP-10, we generated a rabbit antiserum that recognized and neutralized rIP-10 but did not cross-react with any keratinocyte proteins or any other chemokine. Immunoperoxidase staining of normal epidermis demonstrated that IP-10 was expressed by basal but not by differentiated keratinocytes. The epidermis overlying CTCL lesions was often hyperplastic, IP-10 immunostaining was enhanced compared to normal skin, and extended to the suprabasal keratinocytes in 25 of 26 patients for a frequency of 96%; and 95% confidence interval (CI) of 80% to 100%. However, IP-10 was detectable in the dermal or epidermal lymphoid infiltrates in only three of these 26 patients (12%; 95% Cl, 2% to 39%). 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 initially overexpressed before treatment but was normally expressed when he achieved remission. These results suggest 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 proliferation. A better understanding of the growth controls operating in CTCL may be used to develop curative therapies for this disorder.
Sarris
A H
AH
Department's of Hematology, University of Texas M.D. Anderson Cancer Center, Houston 77030, USA.
Daliani
D
D
Ulmer
R
R
Crow
M
M
Broxmeyer
H E
HE
Pugh
W
W
Reiss
M
M
Cabanillas
F
F
Deisseroth
A B
AB
Duvic
M
M
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D054357:Chemokine CXCL10; D019743:Chemokines, CXC / Q000378:metabolism*; D005260:Female; D006801:Humans; D015603:Keratinocytes / Q000378:metabolism*; D016410:Lymphoma, T-Cell, Cutaneous / Q000209:etiology / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000378:metabolism*; D012878:Skin Neoplasms / Q000209:etiology / Q000378:metabolism*
D054357:Chemokine CXCL10; D019743:Chemokines, CXC; D009363:Neoplasm Proteins