Skin-derived interleukin-7 contributes to the proliferation of lymphocytes in cutaneous T-cell lymphoma.
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.
Yamanaka
Kei-ichi
K
Harvard Skin Disease Research Center, Brigham and Women's Hospital, Boston, MA 02115, USA.
Clark
Rachael
R
Rich
Benjamin
B
Dowgiert
Rebecca
R
Hirahara
Kazuki
K
Hurwitz
Daniel
D
Shibata
Michio
M
Mirchandani
Nina
N
Jones
David A
DA
Goddard
Deborah S
DS
Eapen
Sara
S
Mizutani
Hitoshi
H
Kupper
Thomas S
TS
D016022:Case-Control Studies; D049109:Cell Proliferation; D002470:Cell Survival; D002478:Cells, Cultured; D006801:Humans; D015851:Interleukin-7 / Q000097:blood / Q000235:genetics / Q000502:physiology*; D007378:Interleukins / Q000097:blood; D016410:Lymphoma, T-Cell, Cutaneous / Q000209:etiology* / Q000473:pathology; D012333:RNA, Messenger / Q000032:analysis; D012867:Skin; D013601:T-Lymphocytes / Q000473:pathology*
D015851:Interleukin-7; D007378:Interleukins; D012333:RNA, Messenger