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Background: It is well known that fluorouracil (FU) agents frequently induce discoid-lupus-erythematosus (DLE)-like eruptions and acral erythema in Japan. However, the etiology of these drug eruptions caused by FU agents has not been clarified yet. Objective: To determine if the existence of anti-SSA/Ro antibody may be a risk factor for FU-agent-induced DLE-like eruptions and acral erythema. Patients and Methods: Six patients with FU-agent-induced drug eruptions showing DLE-like lesions and acral erythema were enrolled in this study. The titers of anti-SSA/Ro antibody in the sera and the histopathology of the skin lesions were examined. Results: Biopsy specimens from DLE-like eruptions and all 5 examined acral erythema cases showed lichenoid change of the basal keratinocytes. Direct immunofluorescence studies revealed deposition of immunoglobulins along the basement membrane zone in the lesions of both DLE-like eruptions and acral erythema. Further, all 6 cases had high titers of serum anti-SSA/Ro antibody, which did not decline within 6 months after cessation of the causative drug. Conclusion: We propose that anti-SSA/Ro antibody may be a risk factor for FU-agent-induced drug eruptions showing acral erythema and DLE-like eruptions. Copyright © 2007 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

CD4+CD25+ T cells are an important population that plays a crucial role in the maintenance of peripheral self-tolerance. Recently, it was shown that the elimination of these cells by in vivo administration of anti-CD25 monoclonal antibody (mAb) caused the regression of highly immunogenic tumors in syngeneic mice. In this study, we examined whether B16F10 melanoma cells regressed with the elimination of CD25+ regulatory T cells. We found the melanoma cells were not affected at all by in vivo anti-CD25 mAbad ministration alone but tumor rejection resulted in all mice when the administration was combined with IL-12 gene transfer to tumor cells. In vivo, depletion of natural killer (NK) cells or CD8+ T cells cancelled the tumor rejection. NK-cell depletion allowed IL-12-transfected B16F10 melanoma (B16/IL-12) to grow from an early stage and resulted in a more rapid tumor growth of B16/IL-12 than that in mice without administration of anti-CD25 mAb. On the other hand, CD8+ T-cell depletion did not affect the tumor growth in the early phase but allowed B16/IL-12 to grow in rather a late phase and resulted in almost the same degree of tumor growth as in mice without administration of anti-CD25 mAb. In a previous study, we showed that the elimination of CD4+ T cells enhanced the antitumor effect of B16/IL-12 and induced vitiligo-like coat color alteration. Therefore, we also examined the frequency of the change to a vitiligo-like coat color in mice showing tumor rejection caused by CD25+ T-cell elimination to compare with the mechanism enhancing the antitumor effects by cell elimination. The elimination of CD25+ T cells did not induce vitiligo-like coat color changes, though that of CD4+ T cells induced the change in 60%of mice. Furthermore, we confirmed that elimination of CD25+ T cells did not affect the T-helper (Th) 1/Th2 cytokine profile, while that of CD4+ T cells abrogated the Th2 cytokines (IL-4 and IL-10) and resulted in a Th1-dominant cytokine profile in the tumor-draining lymph nodes (TDLNs) of B16/IL-12-bearing mice. These results indicate that in vivo depletion of CD25+ regulatory T cells is a potent useful adjuvant in immunotherapy of B16F10 melanoma, when combined with IL-12 gene transfer and that the enhancement of the antitumor effect by CD25+ T-cell depletion is mediated through CD8+ T cells and may differ from the enhancing mechanism caused by CD4+ T-cell depletion. [ABSTRACT FROM AUTHOR]

Liverand activation-regulated chemokine (LARC)/macrophage inflammatory protein (MIP)-3α/CCL20 is a CC chemokine which is constitutively expressed by follicle-associated epithelial cells in the mucosa, and attracts cells expressing CCR6 such as immature dendritic cells and α4β7high intestine-seeking memory T cells. Here, we examine LARC/CCL20 expression in the skin. LARC/CCL20 mRNA and protein were induced in primary human keratinocytes upon stimulation with proinflammatory cytokines such as IL-1α and tumor necrosis factor (TNF)-α. In mice, intradermal injection of IL-1α and TNF-α rapidly induced a local accumulation of transcripts for LARC/CCL20 and its receptor CCR6 with a lag of several hours in the latter. In humans, immunostaining of LARC/CCL20 was weak if any in normal skin tissues but strongly augmented in lesional skin tissues with atopic dermatitis. Furthermore, massive infiltration of cells with markers such as CD1a, CD3 or HLA-DR was present in atopic skin lesions. Many infiltrating cells were also found to be CCR6+ by a newly generated monoclonal anti-CCR6. However, Langerhans cells residing within the epidermis were hardly stained by anti-CCR6 in normal and atopic skin tissues. Furthermore, plasma levels of LARC/CCL20 were found to be elevated in patients with atopic dermatitis. Collectively, our results suggest that epidermal keratinocytes produce LARC/CCL20 upon stimulation with proinflammatory cytokines such as IL-1α and TNF-α, and attract CCR6-expressing immature dendritic cells and memory/effector T cells into the dermis of inflamed skin such as atopic dermatitis. LARC/CCL20 may not, however, play a major role in homeostatic migration of Langerhans cells into the skin. [ABSTRACT FROM PUBLISHER]

Presents a letter to the editor about chemokines.

A letter to the editor related to a case study of a woman suffering from aspirin-intolerant chronic urticaria is presented.

Summary CD4+ T cells have been reported to suppress immunity against cancer in certain animal models. In this study, we investigated the role of CD4+ T cells in the anti-tumor immune response when interleukin-12-producing melanoma cells are inoculated in mice. We found that interleukin-12-transfected B16 melanoma showed retarded tumor growth in syngeneic mice; however, all the mice developed tumors eventually. In vivo depletion of CD4+ T cells led to complete regression of B16/interleukin-12 tumors in 12 of 20 mice (60%). Immunohistochemical analyses revealed that a number of CD8+ T cells accumulated in close proximity to the B16/interleukin-12 tumors in the CD4+ T cell-depleted mice, whereas CD8+ T cells were only scarcely observed at the periphery of the tumors in control immunocompetent mice. Furthermore, 10 of 20 mice treated with both B16/interleukin-12 inoculation and CD4+ T cell depletion exhibited vitiligo-like coat color alteration. B16/interleukin-12 tumors completely regressed in all the mice with vitiligo. Histologic examination showed that CD8+ lymphocytes accumulated around the hair bulbs of mice with vitiligo, but not in those without vitiligo. These results suggest that CD4+ T cells have an inhibitory effect on tumor rejection by suppressing cytotoxic CD8+ T cells in this melanoma loading model with local interleukin-12 secretion. To investigate the mechanism of enhanced anti-tumor effects by CD4+ T cell depletion, we examined the T helper type 1/2 cytokine profile in the tumor draining lymph nodes of B16/interleukin-12-bearing mice with or without CD4+ T cell depletion using the reverse transcription–polymerase chain reaction method. We found that CD4+ T cell depletion eliminated T helper type 2 cells and resulted in a T helper type 1-dominant cytokine profile in tumor draining lymph nodes. We emphasize that this T helper type 1-dominant cytokine profile may generate further activated CD8+ T cells against B16 melanoma cells, lead B16/interleukin-12 to regress, and result in the destruction of the melanocytes in hair bulbs due to cross-antigenicity between both cell types. This mouse model not only demonstrates the depletion of CD4+ T cells as a useful strategy for cancer gene therapy with interleukin-12 but also provides a model for human melanoma-associated vitiligo.J Invest Dermatol 115:1059–1064 2000. [ABSTRACT FROM AUTHOR]

CD47 is a membrane-associated glycoprotein that suppresses the function of immune cells. We previously reported that Langerhans cells (LCs) express Src homology 2 domain-containing protein tyrosine phosphatase substrate 1 (SHPS-1), a ligand for CD47, which plays an important role in the regulation of their motility. In this study, we show that LCs also express CD47, and that ligation of CD47 with SHPS-1-Fc fusion protein in vivo diminishes the development of the contact hypersensitivity response. We further demonstrate that CD47 engagement affects immune functions of LCs. CD47 engagement in vivo significantly inhibits the emigration of LCs from the epidermis into draining lymph nodes following treatment with haptens and tumor necrosis factor-α. The emigration of dendritic cells from skin explants into the medium and the chemotaxis of murine XS52 dendritic cells were significantly reduced by treatment with SHPS-1-Fc or an anti-CD47 mAb. Under explant culture system, SHPS-1-Fc treatment suppressed the expression of CD80 and CD86 of LCs. These effects on LCs and contact hypersensitivity response of CD47 ligation were reversed by treatment with pertussis toxin. These results suggest that the ligation of CD47 inhibits the migration of LCs and the expression of B7 costimulatory molecules, which results in inhibition of the contact hypersensitivity response.Journal of Investigative Dermatology (2006) 126, 797–807. doi:10.1038/sj.jid.5700176; published online 2 February 2006 [ABSTRACT FROM AUTHOR]

Wheat-dependent exercise-induced anaphylaxis (WDEIA) is a severe IgE-mediated allergic reaction provoked by the combination of wheat-ingestion with intensive physical exercise over the next few hours. Among wheat proteins, ω-5 gliadin, which is one of the components of fast ω-gliadin, has been reported as a major allergen in the anaphylaxis. In this study, we detected IgE-binding epitopes within the primary sequence of ω-5 gliadin using arrays of overlapping peptides synthesized on derivatized cellulose membranes. Sera from four patients with WDEIA having specific IgE to the fast ω-gliadin were used to probe the membrane. Seven epitopes, QQIPQQQ, QQLPQQQ, QQFPQQQ, QQSPEQQ, QQSPQQQ, QQYPQQQ, and PYPP, were detected within the primary sequence of ω-5 gliadin. By using sera of 15 patients, 4 of them, QQIPQQQ, QQFPQQQ, QQSPEQQ, and QQSPQQQ, were found to be dominant epitopes. Mutational analysis of the QQIPQQQ and QQFPQQQ indicated that amino acids at positions Gin¹, Pro4, Gln5, Gln6, and Gln7 were critical for IgE binding. These results will provide a useful tool for developing safer wheat products in addition to diagnostic and immunotherapy techniques for WDEIA. [ABSTRACT FROM AUTHOR]

A seven month-old boy had been suffering from recalcitrant pompholyx of both soles in spite of the treatment with corticosteroid ointment for three months. Because patch test of chromium was positive at 48 and 96 hr reading, we advised to his mother that the infant must avoid to touch and to take the chromium-containing goods. His lactating mother had been taking high amounts of chocolate and cocoa every day, both of which contain considerable amounts of chromium. The pompholyx disappeared within 2 weeks, after his mother stopped eating chocolate and cocoa. Oral provocation test with chocolate and cocoa to the patient's lactating mother resulted in the development of pompholyx in the baby within two days. We diagnosed the infant as systemic metal allergy to chromium which was possibly transferred from his mother's milk. This is the first report of systemic metal allergy which is provoked by mother's milk which is from the person who takes a lot of metal-containing foods.

Background: A number of cases of oral allergy syndrome (OAS) to fruits with birch pollinosis have been described. The antigen of Alnus sieboldiana (alder) trees which are massively planted on Rokko Mountain appeared to be highly similar to birch pollen., Methods: We took the medical history of pollinosis and OAS, measured pollen-specific IgE (CAP-RAST) and performed prick tests of causative fruits to the outpatients of the two hospitals in different areas., Result: In Hanshinkan district, at the foot of Rokko Mountain, we experienced 9 cases of OAS among 377 outpatients. All 9 cases had alder specific-IgE. The prevalence rate of OAS was 11.0% in the alder specific-IgE-positive patients and 0% in the alder specific-IgE-negative patients in the area. On the other hand, in Higashiharima district where less alder trees exist and further from Rokko Mountain, 19 OAS patients were documented among 2000 outpatients. Six of the 19 patients with OAS did not have alder specific-IgE. The prevalence rate of OAS was 6.8% in the alder specific-IgE-positive patients and 11.8% in the mugwort specific-IgE-positive patients in the area., Conclusion: In Hanshinkan, alder pollinosis seems to be most important for the cross reactivity to the OAS. In Higashiharima, mugwort pollinosis may be more important than alder pollinosis for the cross reactivity to the OAS.