Interactions between chemokines and chemokine receptors are involved in migration and invasion of lymphoma cells. We investigated expression profiles of CXCR3 and CCR4 by immunohistochemistry and flow cytometry, and their biologic behaviors by real-time horizontal chemotaxis assay in cutaneous T cell and NK/T-cell lymphomas (TCLs). Tumor cells in mycosis fungoides (MF) constantly expressed CXCR3 at the patch stage, and expressed CCR4 at the tumor stage and in the folliculotropic variant of MF. Neoplastic cells at the plaque stage expressed CXCR3 and/or CCR4. Sezary cells in the dermis and circulation were positive for CCR4. Epidermotropic atypical cells in pagetoid reticulosis expressed CXCR3. CD30 cells exclusively expressed CCR4 in anaplastic large-cell lymphoma, and CXCR3 and/or CCR4 in lymphomatoid papulosis. In CD8TCL and extranodal NK/TCL characterized by extensive epidermotropism, tumor cells were positive for CXCR3. These data demonstrated preferential expression of CXCR3 in epidermotropic tumor cells, and of CCR4 in dermis-based lymphomas. In chemotaxis assays, CCR4 tumor cells in MF and CXCR3 tumor cells in CD8TCL migrated to thymus and activation-regulated chemokine and inducible protein-10, respectively. Therefore, spatial and temporal interactions between chemokine receptors and their ligands seem to dictate recruitment and retention of lymphoma cells in the skin.

The patients with AD had higher anxiety levels than normal individuals, and those with a stronger perception of TA than SA showed enhanced serum IgE synthesis and Th2 shifting.

Percutaneous peptide immunization (PPI) is a simple and noninvasive immunization approach to induce potent CTL responses by peptide delivery via skin with the stratum corneum removed. After such a barrier disruption in human skin, epidermal Langerhans cells, although functionally matured through the up-regulation of HLA expression and costimulatory molecules, were found to emigrate with a reduced number of dendrites. CD8+ populations binding to MHC-peptide tetramers/pentamers and producing IFN-; appeared in the blood after PPI with HLA class I-restricted antigenic peptides. PPI with melanoma-associated peptides reduced the lesion size and suppressed further development of tumors in four of seven patients with advanced melanoma. These beneficial effects were accompanied by the generation of circulating CTLs with in vitro cytolytic activity and extensive infiltration of tetramer/pentamer-binding cells into regressing lesions. PPI elicited neither local nor systemic toxicity or autoimmunity, except for vitiligo, in patients with melanoma. Therefore, PPI represents a novel therapeutic intervention for cancer in the clinical setting.

Atopic dermatitis (AD) is a pruritic, chronically relapsing skin disease in which Th2 cells play a crucial role in cutaneous and extracutaneous immune reactions. In humans, CD11c+CD123− myeloid dendritic cells (mDC) and CD11c−CD123+ plasmacytoid DC (pDC) orchestrate the decision-making process in innate and acquired immunity. Since the number and function of these blood dendritic cell (DC) subsets reportedly reflect the host immune status, we studied the involvement of the DC subsets in the pathogenesis of AD. Patients with AD had an increased DC number and a low mDC:pDC ratio with pDC outnumbering mDC in the peripheral blood compared with normal subjects and psoriasis patients (a Th1 disease model group). The mDC:pDC ratio was correlated with the total serum IgE level, the ratio of IFN-γ-producing blood cells:IL-4-producing blood cells, and the disease severity. In vitro allogeneic stimulation of naive CD4+ cells with atopic DC showed that the ability of pDC for Th1 induction was superior or comparable to that of mDC. In skin lesions, pDC infiltration was in close association with blood vessels expressing peripheral neural addressins. Therefore, compartmental imbalance and aberrant immune function of the blood DC subsets may deviate the Th1/Th2 differentiation and thus induce protracted allergic responses in AD.

Sir.Palpable archiform migratory erythema (PAME) is a rare member of the family of T-cell pseudolymphomas occurring preferentially in adull males ( I -5 ). The clinical picture of PAME is distinctive from other pseudolymphomas because infiltrated annular erythema develops into elevated migrating lesions in the trunk as the predilection site. The aetiology of this condition is unknown and the disease runs a chronic course. We report here a case of PAME in which polyclonal populations of T cells proliferated surrounding a preceding B-cell pseudolymphoma. CASE REPORTA 66-year-old man h;id developed a red, small lump iO years previously and after 7 years arc-shaped eruptions began to appear surrounding this initial lesion. The initial examination revealed an indurated smooth surfaced nodule 2.5 cm in diameter surrounded hy arcbitbrm and annular, firm, palpable erythemas on the back (Fig, la). Tbere were no subjective symptoms or superficial lymphadenopathy. The central nodule gradually resolved in 3 months after the first visit to our clinic without any treatment. The archiforEii and annular erythemas waxed and waned, as a part of the lesions disappeared in 2-3 months while other parts tended to clear, without any systemic or topical treatment (Fig. Ib). While oral penicillin, topical steroids of strong potency, and intra-lesional and intravenous injections of interferon-Y(6) were ineffective, oral administration of prednisolone at a starting dose of 30 mg/day follov^-ed by dose-tapering completely cleared the lesions in 8 months.Laboratory findings including red and white blood cell counts, haemoglobin levels, serum electrolytes, liver enzyme levels.serum protein and immunoglobulin levels and C-reactive protein were normal on several occasions during our 3-ycar observation. Anti-nuclear antibodies, and antibodies to Trcponenuipalliilum, human T-lympholrople virus-1, human immunodetlciency virus, hepatitis C virus, and Borrelia hurgihrferi were always negative. Chest X-ray showed no abnormality, and there was no lyinphadenopathy or hepatosplenomegaly hy computerized tomography scanning. Bone marrow aspiration revealed normal cellular composition.In the central nodule, atypical lymphoid cells with large, irregularly shaped, pale nuclei and small lymphocytes lay either intermingled with one another or in a follicular arrangement in the entire upper dermis (Fig, 2a). Lymphoid follicular structures consisted of CD20' large atypical B and CD3' small T cells at a ratio of 9:1 (Fig, 2b). At resolution, mononuclear cell infiltrates localized to perivascular areas with less conspicuous follicular structures that consisted of almost equal numbers of CD20' and CD3' cells. Specimens obtained from arciform erythema on 3 occasions at different siles consistently revealed a dense lymphocytic infiltrate around the blood vessels and hair follicles in the upper and mid dermis, with a CD3 ' to CD20" cell ratio of 7 to 3 (Fig, 3). No follicular structure was apparent. In addition, helper T cells outnumbered cytotoxic T cells since CD4" ...