T-cell clones from early-stage cutaneous T-cell lymphoma show no polarized Th-1 or Th-2 cytokine profile.
Recent studies of the cytokine pattern in skin lesions of patients with cutaneous T-cell lymphoma (CTCL) have shown that interleukin-4 (IL-4) and Il-10, both cytokines produced by T-helper type 2 cells, dominate in these lesions. Also, in single studies, interferon-gamma (IFN-gamma), a major cytokine of Th-1-cells, has been found to be absent. Consequently, it has been hypothesized that immune-suppressive Th-2 cytokines may promote local growth of the malignant lymphocyte clone. However, there is so far no evidence for T-cells as the source of the Th-2 cytokines in CTCL skin lesions nor have these cytokines been investigated at a clonal T-cell level. We established a total of 120 T-cell clones (TCCs) from lesional skin and 54 TCCs from the blood of four patients with mycosis fungoides. Epidermal TCCs (mostly CD8-positive) and dermal TCCs (mostly CD4-positive) were stimulated by the mitogen concanavalin A and, seeking a polarized cytokine pattern, the supernatants were assessed by ELISA. We showed that the vast majority of TCCs were able to secrete IFN-gamma and IL-4. IFN-gamma-deficient TCCs occurred only in the epidermis. Some (18) TCCs were found to be either negative for IL-10 production or to produce low levels only. No significant differences were observed between blood- and skin-derived TCCs. Thus a polarized Th-2 cytokine pattern was not detectable among cultured skin-infiltrating nonmalignant T-cells (TILs) isolated from early mycosis fungoides. It therefore appears unlikely that Th-2-mediated immune suppression is a major mechanism operating in early CTCL. However, this does not exclude its role in late-stage disease.
Harwix
S
S
Department of Dermatology, Göttingen University, von-Siebold-Str. 3, 37075 Göttingen, Germany.
Zachmann
K
K
Neumann
C
C
D000368:Aged; D016516:CD4-CD8 Ratio; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology; D002999:Clone Cells; D016207:Cytokines / Q000378:metabolism*; D005260:Female; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D015847:Interleukin-4 / Q000378:metabolism; D016410:Lymphoma, T-Cell, Cutaneous / Q000097:blood / Q000235:genetics / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D012867:Skin / Q000473:pathology; D012878:Skin Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D013601:T-Lymphocytes / Q000737:chemistry / Q000166:cytology*; D018417:Th1 Cells / Q000737:chemistry / Q000166:cytology*; D018418:Th2 Cells / Q000737:chemistry / Q000166:cytology*
D016207:Cytokines; D015847:Interleukin-4; D007371:Interferon-gamma