Antigen-specific CD8 T cells can eliminate antigen-bearing keratinocytes with clonogenic potential via an IFN-γ-dependent mechanism

The immune system surveys the skin for keratinocytes (KCs) infected by viruses or with acquired genetic damage. The mechanism by which T cells mediate KC elimination is however undefined. In this study we show that antigen-specific CD8 T cells can eliminate antigen-bearing KCs in vivo and inhibit their clonogenic potential in vitro, independently of the effector molecules perforin and Fas-ligand (Fas-L). In contrast, IFN-gamma receptor expression on KCs and T cells producing IFN-gamma are each necessary and sufficient for in vitro inhibition of KC clonogenic potential. Thus, antigen-specific cytotoxic T lymphocytes (CTLs) may mediate destruction of epithelium expressing non-self antigen by eliminating KCs with potential for self-renewal through an IFN-gamma-dependent mechanism

Antigen-specific CD4 cells assist CD8 T-effector cells in eliminating keratinocytes

Keratinocytes expressing tumor or viral antigens can be eliminated by antigen-primed CD8 cytotoxic T cells. CD4 T-helper cells help induction of CD8 cytotoxic T cells from naive precursors and generation of CD8 T-cell memory. In this study, we show, unexpectedly, that CD4 cells are also required to assist primed CD8 effector T cells in rejection of skin expressing human growth hormone, a neo-self-antigen, in keratinocytes. The requirement for CD4 cells can be substituted by CD40 costimulation. Rejection of skin expressing ovalbumin (OVA), a non-self-antigen, by primed CD8 cytotoxic T cells can in contrast occur without help from antigen-specific CD4 T cells. However, rejection of OVA expressing keratinocytes is helped by antigen-specific CD4 T cells if only low numbers of primed or naive OVA-specific CD8 T cells are available. Effective immunotherapy directed at antigens expressed in squamous cancer may therefore be facilitated by induction of tumor antigen-specific CD4 helper T cells, as well as cytotoxic CD8 T cells

Toxic Epidermal Necrolysis after Pemetrexed and Cisplatin for Non-Small Cell Lung Cancer in a Patient with Sharp Syndrome

Background: Pemetrexed is an antifolate drug approved for maintenance and second-line therapy, and, in combination with cisplatin, for first-line treatment of advanced nonsquamous non-small cell lung cancer. The side-effect profile includes fatigue, hematological and gastrointestinal toxicity, an increase in hepatic enzymes, sensory neuropathy, and pulmonary and cutaneous toxicity in various degrees. Case Report: We present the case of a 58-year-old woman with history of Sharp's syndrome and adenocarcinoma of the lung, who developed toxic epidermal necrolysis after the first cycle of pemetrexed, including erythema, bullae, extensive skin denudation, subsequent systemic inflammation and severe deterioration in general condition. The generalized skin lesions occurred primarily in the previous radiation field and responded to immunosuppressive treatment with prednisone. Conclusion: Although skin toxicity is a well-known side effect of pemetrexed, severe skin reactions after pemetrexed administration are rare. Caution should be applied in cases in which pemetrexed is given subsequent to radiation therapy, especially in patients with pre-existing skin diseases

Excretory/Secretory-Products of Echinococcus multilocularis Larvae Induce Apoptosis and Tolerogenic Properties in Dendritic Cells In Vitro

Parasitic helminths are inducers of chronic diseases and have evolved mechanisms to suppress the host immune response. Mostly from studies on roundworms, a picture is currently emerging that helminths secrete factors (E/S-products) that directly act on sentinels of the immune system, dendritic cells, in order to achieve an expansion of immunosuppressive, regulatory T cells (T-reg). Parasitic helminths are currently also intensely studied as therapeutic agents against autoimmune diseases and allergies, which is directly linked to their immunosuppressive activities. The immunomodulatory products of parasitic helminths are therefore of high interest for understanding immunopathology during infections and for the treatment of allergies. The present work was conducted on larvae of the tapeworm E. multilocularis, which grow like a tumor into surrounding host tissue and thus cause the lethal disease alveolar echinococcosis. The authors found that E/S-products from early infective larvae are strong inducers of tolerogenic DC in vitro and show that E/S-products of larvae of the chronic stage lead to an in vitro expansion of Foxp3+ T cells, suggesting that both the expansion of these T cells and poorly responsive DC are important for the establishment and persistence of E. multilocularis larvae within the host

7th Drug hypersensitivity meeting: part two

No abstract availabl

Reversible cobalt-carbon bond formation in catalytic chain transfer polymerization

The reversible bond formation between cobalt(II) catalytic chain transfer agents and propagating radicals was studied using electron paramagnetic resonance and conventional kinetic measurements. It was found that this reversible cobalt-carbon bond formation has no significant effect on the catalytic chain transfer polymerization of methyl methacrylate but does affect the polymerization behavior of styrene. In both systems significant induction periods are observed which seem to disappear in the methyl methacrylate system but persist in the styrene system upon decreasing the initial concentration of the cobalt(II) complex. The overall rates of polymerizations are found to be readily described by "classical" free-radical polymerization kinetics, including a chain-length-dependent average termination rate coefficient. Furthermore, in contrast to the situation observed in methyl methacrylate polymerization where constant molecular weights are produced over the entire conversion range, it was found that the molecular weight in styrene increases with conversion until a constant molecular weight is obtained which is given by the Mayo equation. The kinetic behavior and the molecular weight evolution could simply be modeled by a reaction scheme providing a constant radical concentration and the presence of a chain transfer agent