Epidermal interferon-gamma inducible protein-10 (IP-10) and monokine induced by gamma-interferon (Mig) but not IL-8 mRNA expression is associated with epidermotropism in cutaneous T cell lymphomas.

Epidermal infiltration by neoplastic CD4+ T cells is a characteristic 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 chemokines IL-8 and interferon-gamma inducible protein 10 (IP-10) may play a role, but evidence that these chemokines are produced within the epidermis in epidermotropic CTCL is lacking. In this study skin biopsies from 17 CTCL patients, including 12 mycosis fungoides, four pleomorphic CTCL, and one CD8+ CTCL, were investigated for epidermal IL-8 and IP-10 mRNA expression by RNA in situ hybridization. In addition, the expression of monokine induced by gamma-interferon (Mig) mRNA, a CXC chemokine closely related to IP-10, was studied as well. The expression of IL-8 receptors A and B (CXCR1 and CXCR2, respectively) was investigated by immunohistochemistry. The results were correlated with the number and phenotype of epidermotropic T cells. Epidermal expression of IP-10 and Mig mRNA was detected in 10 of 11 and seven of 11 epidermotropic CTCL, respectively, but not in five nonepidermotropic CTCL biopsies or normal human skin. Epidermal IP-10 and Mig mRNA expression correlated 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 of neutrophils. Consistently, immunostaining of the (intraepidermal) T cells with antibodies against CXCR1 and CXCR2 was not observed. In conclusion, the results of this study indicate that IP-10, and to a lesser extent Mig, but not IL-8 is involved in the preferential infiltration of neoplastic CD4+ T cells in CTCL.

Absence of T(H)2 cytokine messenger RNA expression in CD30-negative primary cutaneous large T-cell lymphomas.

BACKGROUND: Previous studies demonstrating that the neoplastic cells in Sézary syndrome and tumor stage mycosis fungoides express interleukin 4 (IL-4), IL-5, and IL-10 have resulted in the concept that cutaneous T-cell lymphomas are derived from CD4(+) T cells with a T(H)2 type cytokine profile. OBJECTIVE: To determine the cytokine profile in CD30(-) primary cutaneous large T-cell lymphomas, which represent a subgroup of cutaneous T-cell lymphoma with an aggressive clinical behavior (5-year survival rate of 15%). DESIGN AND METHODS: Seven biopsy specimens were taken from 4 patients with CD30(-) primary cutaneous large T-cell lymphomas and studied for the expression of T(H)1 (IL-2 and interferon gamma) and T(H)2 (IL-4, IL-5, IL-10) cytokines using a reverse transcription-polymerase chain reaction technique. Skin biopsy specimens from patients with Sézary syndrome, mycosis fungoides, atopic dermatitis, or psoriasis were included as controls. RESULTS: In the 7 CD30(-) primary cutaneous large T-cell lymphomas showing an almost pure population of large tumor cells (>90%), no expression of IL-4 was found, and IL-5 was only found in 1 of 7 cases. In control biopsy specimens, expression of IL-4 and/or IL-5 was demonstrated in atopic dermatitis (3/3), tumor stage mycosis fungoides (2/2), and Sézary syndrome (3/3), but not in plaque stage mycosis fungoides. CONCLUSION: Our results demonstrate that CD30(-) primary cutaneous large T-cell lymphomas do not produce T(H)2 cytokines, illustrating that not all cutaneous T-cell lymphomas have a T(H)2 cytokine profile.