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 Blood, 15 March 2006, Vol. 107, No. 6, pp. 2440-2445.
Prepublished online as a Blood First Edition Paper on December 1, 2005; DOI 10.1182/blood-2005-03-1139.

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IMMUNOBIOLOGY

Skin-derived interleukin-7 contributes to the proliferation of lymphocytes in cutaneous T-cell lymphoma

Kei-ichi Yamanaka, Rachael Clark, Benjamin Rich, Rebecca Dowgiert, Kazuki Hirahara, Daniel Hurwitz, Michio Shibata, Nina Mirchandani, David A. Jones, Deborah S. Goddard, Sara Eapen, Hitoshi Mizutani, and Thomas S. Kupper

From the Harvard Skin Disease Research Center, Department of Dermatology, Brigham and Women's Hospital, Boston, MA; Department of Dermatology, Mie University, Graduate School of Medicine, Japan; and Biostatistics Core Facility, Dana Farber Harvard Cancer Center, Department of Biostatistics, Dana-Farber Cancer Institute, Boston, MA.

Cutaneous T-cell lymphomas (CTCLs) are malignancies of T cells that have a special affinity for the skin. We have previously reported that much of the T-cell receptor repertoire is altered in CTCL, and both malignant and nonmalignant clones are numerically expanded, presumably in response to T-cell trophic cytokines. We therefore examined levels of the T-cell trophic cytokines IL-2, IL-4, IL-7, IL-12, IL-13, and IL-15 in plasma in 93 CTCL patients and healthy controls. Only IL-7 levels were elevated in CTCL. We next looked at lesional skin from patients with CTCL and found elevated levels of IL-7 mRNA. Explant cultures of normal and lesional CTCL skin biopsies revealed significantly more IL-7 protein production in CTCL skin. Additionally, cultures of CTCL skin released greater numbers of T cells than normal skin; this was blocked by the addition of an IL-7 neutralizing antibody. Finally, these cultures induced proliferation of normal peripheral skin-homing T cells that were added to the cultures. These observations led us to postulate that IL-7 produced by skin cells contributes to the survival and proliferation of T cells within skin lesions and is likely the source of elevated circulating IL-7 in CTCL. (Blood. 2006;107:2440-2445)


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