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Acute generalized exanthematous pustulosis (AGEP) is a diffuse pustular disorder that usually begins in intertriginous folds with widespread erythema. The causes in the majority of the cases are drugs. T cells and interleukin (IL)-8 play roles in the development of AGEP, but the mechanism remains to be elucidated. We investigated the involvement of Th17 cells and their cytokine IL-22 in the pathogenesis. Three patients with AGEP were enrolled in this study. The percentages of IL-17 Th17 cells, interferon γ T cells and IL-4 T cells were measured in the patients' peripheral blood lymphocytes by intracellular cytokine staining and flow cytometry. The concentration of IL-22 in the sera was measured by enzyme-linked immunosorbent assay. The percentages of Th17 cells were markedly higher in all three patients than healthy control individuals. The frequencies of interferon γ T cells were slightly high in the patients compared with the control, and there was no definite tendency in IL-4 T-cell frequencies. The concentration of IL-22 was remarkably high in all patients when compared with normal subjects with levels under detection. Th17 cells and their produced cytokine IL-22 were elevated in the peripheral blood of patients with AGEP. As IL-17 and IL-22 cooperatively stimulate keratinocytes to produce IL-8, IL-8 may contribute to the accumulation of neutrophils in the lesional epidermis of AGEP. [ABSTRACT FROM AUTHOR]

CD27 is a T-cell surface antigen expressed on the majority of peripheral T cells and belongs to a newly defined receptor family including the iow-affinity nerve growth factor receptor, tumour necrosis factor (TNF) receptors, the B-cell activation antigen CD40, and the Fas antigen. Although the function of CD27 has not been defined, several experimental observations support the notion that this molecule plays an important role in the process of T-cell activation. In this paper, we have demonstrated that a rapid hyperphosphorylation of CD27 is induced by a cyclic AMP-inducing agent, forskolin, and a membrane-permeable cAMP analogue, 8-bromo-cAMP, as well as phorbol 12-myristate 13-acetate (PMA). In addition, increased phosphorylation of CD27 in T-cell activation either via CD2 or CD3 pathways was strongly suppressed by a cyclic nucleotide-dependent kinase inhibitor, H-8, but only slightly by a protein kinase C inhibitor, staurosporine. These results suggest that protein kinase A might be a key kinase responsible for CD27 phosphorytation in the process of T-cell activation. CD27 is the first T-cell surface antigen demonstrated to be phosphorylated by the cyclic AMP-protein kinase A-mediated pathway. [ABSTRACT FROM AUTHOR]

A 31-year-old man had had atopic dermatitis since childhood and developed vitiligo with inflammatory raised borders 5 years prior to presentation. Immunohistochemically, CD4+ T cells infiltrated predominantly in the raised border of vitiligo, while CD8+ T cells were present just outside of the borders, suggesting that CD8+ cells were an antecedent to the CD4+ cells. Despite the presence of atopic dermatitis, the percentage of CXCR3+ CD4+ Th1 cells increased in the patient's peripheral blood, compared with a representative atopic patient showing a high percentage of CCR4+CD4+ Th2 cells. This case suggests that vitiligo with inflammatory raised borders can occur even in patients with atopic dermatitis when Th1 cells are activated and overcome the Th2-dominant state. [ABSTRACT FROM AUTHOR]

The article presents a case study of a patient suffering with Nagashima-type keratosis palmoplantaris (PPK). The histological examination shows a mild to moderate infiltrate of mononuclear cells in the dermal papillae and shows that the pathogenesis may be related to the effects of T cells infiltrating into the skin. The patient is treated with betamethasone valerate ointment and tacrolimus ointment, which shows improvement of erythematous hue and hyperkeratosis in both hands.

t(17;19)-acute lymphoblastic leukemia (ALL) shows extremely poor prognosis. E2A-HLF derived from t(17;19) blocks apoptosis induced by the intrinsic mitochondrial pathway and has a central role in leukemogenesis and chemoresistance. Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is expressed on cytotoxic T cells and natural killer cells and binds with death receptors (DR4/DR5), inducing apoptosis by dual activation of intrinsic and extrinsic pathways, and TRAIL mediates the graft-versus-leukemia (GVL) effect after allogeneic stem cell transplantation (allo-SCT). We found that cell lines and patients' samples of t(17;19)-ALL expressed death receptors for TRAIL, and recombinant soluble TRAIL immediately induced apoptosis into t(17;19)-ALL cell lines. E2A-HLF induced gene expression of DR4/DR5, which was dependent on the DNA-binding and transactivation activities of E2A-HLF through the 5′ upstream region of the start site at least in the DR4 gene. Introduction of E2A-HLF into non-t(17;19)-ALL cell line upregulated DR4 and DR5 expression, and sensitized to proapoptotic activity of recombinant soluble TRAIL. Finally, a newly diagnosed t(17;19)-ALL patient underwent allo-SCT immediately after induction of first complete remission, and the patient has survived without relapse for over 3-1/2 years after allo-SCT. These findings suggest that E2A-HLF sensitizes t(17;19)-ALL to the GVL effect by upregulating death receptors for TRAIL. [ABSTRACT FROM AUTHOR]