EPIDERMAL INTERFERON-GAMMA INDUCIBLE PROTEIN-10 (IP-10) AND MONOKINE INDUCED BY GAMMA-INTERFERON (MIG) BUT NOT IL-8 MESSENGER-RNA EXPRESSION IS ASSOCIATED WITH EPIDERMOTROPISM IN CUTANEOUS T-CELL LYMPHOMAS

Epidermal infiltration by neoplastic CD4(+) T cells is a characteristi c histologic feature of early stage mycosis fungoides, the most common type of cutaneous T cell lymphoma (CTCL), The mechanisms involved in epidermotropism are unknown. It has been suggested that the CXC chemok ines IL-8 and interferon-gamma inducible protein 10 (IP-10) may play a role, but evidence that these chemokines are produced within the epid ermis in epidermotropic CTCL is lacking. In this study skin biopsies f rom 17 CTCL patients, including 12 mycosis fungoides, four pleomorphic CTCL, and one CD8(+) CTCL, were investigated for epidermal IL-8 and I P-10 mRNA expression by RNA in situ hybridization, In addition, the ex pression of monokine induced by gamma-interferon (Mig) mRNA, a CXC che mokine closely related to IP-10, was studied as well. The expression o f IL-8 receptors A and B (CXCR1. and CXCR2, respectively) was investig ated by immunohistochemistry. The results were correlated with the num ber and phenotype of epidermotropic T cells. Epidermal expression of I P-10 and Mig mRNA was detected in 10 of 11 and seven of 12 epidermotro pic CTCL, respectively, but not in five nonepidermotropic CTCL biopsie s or normal human skin, Epidermal IP-10 and Mig mRNA expression correl ated with epidermal infiltration of CD4(+) T cells, but not of CD8(+) T cells. IL-8 mRNA was demonstrated in the epidermis of only two of 15 CTCL biopsies, and was associated, in both cases, with accumulation o f neutrophils. Consistently, immunostaining of the (intraepidermal) T cells with antibodies against CXCR1 and CXCR2 was not observed. In con clusion, the results of this study indicate that IP-10, and to a lesse r extent Mig, but not IL-8 is involved in the preferential infiltratio n of neoplastic CD4(+) T cells in CTCL.