CYTOKINE LOOPS INVOLVING INTERFERON-GAMMA AND IP-10, A CYTOKINE CHEMOTACTIC FOR CD4(+) LYMPHOCYTES - AN EXPLANATION FOR THE EPIDERMOTROPISM OF CUTANEOUS T-CELL LYMPHOMA
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SARRIS, AH
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机构:UNIV TEXAS,MD ANDERSON CANC CTR,DEPT MED SPECIALTIES,HOUSTON,TX 77030
SARRIS, AH
ESGLEYESRIBOT, T
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机构:UNIV TEXAS,MD ANDERSON CANC CTR,DEPT MED SPECIALTIES,HOUSTON,TX 77030
ESGLEYESRIBOT, T
CROW, M
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机构:UNIV TEXAS,MD ANDERSON CANC CTR,DEPT MED SPECIALTIES,HOUSTON,TX 77030
CROW, M
BROXMEYER, HE
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机构:UNIV TEXAS,MD ANDERSON CANC CTR,DEPT MED SPECIALTIES,HOUSTON,TX 77030
BROXMEYER, HE
KARASAVVAS, N
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KARASAVVAS, N
PUGH, W
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机构:UNIV TEXAS,MD ANDERSON CANC CTR,DEPT MED SPECIALTIES,HOUSTON,TX 77030
PUGH, W
GROSSMAN, D
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GROSSMAN, D
DEISSEROTH, A
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DEISSEROTH, A
DUVIC, M
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机构:UNIV TEXAS,MD ANDERSON CANC CTR,DEPT MED SPECIALTIES,HOUSTON,TX 77030
DUVIC, M
机构:
[1] UNIV TEXAS,MD ANDERSON CANC CTR,DEPT MED SPECIALTIES,HOUSTON,TX 77030
[2] UNIV TEXAS,MD ANDERSON CANC CTR,DEPT PATHOL,HOUSTON,TX 77030
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 role in the epidermotropism of cutaneous T-cell lymphoma (CTCL) that is known to express IFN-gamma mRNA in the epidermis and is characterized by an indolent course with multiple relapses that remain confined to the skin for many years. By injecting purified recombinant (r) IP-10 we generated a polyclonal rabbit antiserum that specifically recognized and neutralized rIP-10. With immunoperoxidase staining, IP-10 expression was limited to the basal epidermal keratinocytes of normal skin. In biopsies of CTCL lesions the expression of IP-10 was markedly increased and it extended to the suprabasal keratinocytes in 17 of 18 patients, but it was detectable only faintly in the dermal or epidermal lymphoid infiltrates in 2 of these 18 patients. In 1 patient who had matching biopsies performed before and after treatment, IP-10 was overexpressed before treatment, but was normally expressed in the posttreatment biopsy that showed resolution of the CTCL. Increased IP-10 expression was not detected in any of 4 patients with B-cell lymphoma involving the dermis. On the basis of these findings and a review of the literature, we propose that secretion of IFN-gamma by the lymphoid infiltrate in CTCL induces the epidermal keratinocytes to secrete IP-10 that, in turn, is chemotactic for CTCL, accounting for its epidermotropism. This model may be used as a basis for future investigations of the pathogenesis of CTCL. (C) 1995 by The American Society of Hematology.