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Background Delayed allergic hypersensitivity reactions have classically been described as type IV reactions, which are caused by T cells; however, the respective roles of CD4+ and CD8+ cells are yet to be defined. A central role for CD8+ cytotoxic T cells as effector cells has been suggested. Objectives To determine the type of T cell involved in corticosteroid allergy. Methods We analysed the kinetics of T cell recruitment and the cytokine production profile in positive patch tests of 27 corticosteroid-sensitized patients, as compared with control sites and control subjects. Skin biopsies, collected at 8, 24 and 48 hr following drug application, were embedded in paraffin for histological and immunohistological staining, and, in some cases, also deep-frozen for gene expression analyses. Results CD3+ T cells were rapidly recruited in concert with the positivity of the patch test sites. High levels of interleukin (IL)-4, IL-5 and, to a lesser extent, interferon- γ suggested that both Th2 and Th1 cytokines were implicated. IL-4 was also produced by γδ T cell receptor (TCR) lymphocytes. Conclusions This study showed that, in allergic contact dermatitis caused by corticosteroids, the inflammatory infiltrate is composed of CD3+ T cells with a predominant Th2 cytokine profile, among which IL-4 is also produced by γδ TCR lymphocytes. [ABSTRACT FROM AUTHOR]

The human suppressive T cells that stably express transcription factor FOXP3, or regulatory T cells (Tregs), are thought to suppress antitumor immune responses. The most specific marker for human Tregs is the demethylation of CpG dinucleotides located in the first intron of FOXP3 ( FOXP3i1). FOXP3i1 is completely methylated in other hematopoietic cells, including nonsuppressive T cells that transiently express FOXP3 after activation. Previously, we and others reported estimations of the frequency of Tregs in the blood of melanoma patients using a FOXP3i1 methylation-specific qPCR assay. Here, we attempted to quantify Tregs inside tumor samples using this assay. However, we found demethylated FOXP3i1 sequences in the melanoma cells themselves. This demethylation was not associated with substantial FOXP3 mRNA or protein expression, even though the demethylation extended to the promoter and terminal regions of the gene in some melanoma cells. Our results imply that analyzing Treg frequencies by quantification of demethylated FOXP3i1 will require that tumor-infiltrating T cells be separated from melanoma cells. [ABSTRACT FROM AUTHOR]

We report that melanoma cell lines expressing the interleukin-1 receptor exhibit 4- to 10-fold lower levels of mRNA of microphthalmia-associated transcription factor ( MITF- M) when treated with interleukin-1β. This effect is NF-κB and JNK-dependent. MITF-M regulates the expression of melanocyte differentiation genes such as MLANA, tyrosinase and gp100, which encode antigens recognized on melanoma cells by autologous cytolytic T lymphocytes. Accordingly, treating some melanoma cells with IL-1β reduced by 40-100% their ability to activate such antimelanoma cytolytic T lymphocytes. Finally, we observed large amounts of biologically active IL-1α or IL-1β secreted by two melanoma cell lines that did not express MITF-M, suggesting an autocrine MITF-M downregulation. We estimate that ∼13% of melanoma cell lines are MITF-M-negative and secrete IL-1 cytokines. These results indicate that the repression of melanocyte-differentiation genes by IL-1 produced by stromal cells or by tumor cells themselves may represent an additional mechanism of melanoma immune escape. [ABSTRACT FROM AUTHOR]

Evaluates the responses of cancer patients vaccinated with a melanoma antigen-3 antigenic peptide or a recombinant virus coding for peptide aimed at establishing whether there is a correlation between tumoral regressions and T-cell responses against vaccine antigen. Characteristics of the normal anti-melanoma antigen-3.A1 (anti-MAGE-3.A1) repertoir; Detection of anti-MAGE-3.A1 T-cell responses; Analysis of vaccinated patients.

A letter to the editor is presented on the active immunotherapy for the treatment of cancer.