New insights in the pathogenesis of atopic disease.

A causal link between the increasing environmental pollution and the fast spreading of allergic diseases is currently discussed. The exogenic and endogenic noxious agents contributing to the total environmental load are primarily acting through immunotoxic, sensitizing and neurotoxic mechanisms in animal experiments and in humans. Beside classic allergic-triggering factors (allergen potency, intermittent exposure to different allergen concentrations, presence of microbial bodies and sensitizing phenols), the adjuvant role of environmental pollutants gains increasing importance in allergy induction.

Increased levels of transition metals in breast cancer tissue.

Objectives: High levels of transition metals such as iron, nickel, chromium, copper, and lead are closely related to free radical generation, lipid peroxidation, formation of DNA strand breaks, and tumor growth in cellular systems. In order to determine the correlation to malignant growth in humans, we investigated the accumulation of heavy metals in 20 breast cancer biopsies and compared the findings to the levels found in 8 healthy biopsies.

Methods: The concentration of transition metals in breast cancer and control biopsies was assessed by a standardized Atomic Absorption Spectrofotometry technique with acidic hydrolysis for sample preparation.

T cell development in mice expressing splice variants of the protein tyrosine phosphatase CD45.

The transmembrane protein tyrosine phosphatase CD45 is expressed in multiple isoforms as a result of alternative splicing of variable exons encoding the extracellular domain. CD45 expression is critical for T cell development, and thymocyte maturation is blocked at the immature CD4+ CD8+ double-positive stage in CD45 gene-deficient (CD45 -/-) mice. Moreover, splicing of variable CD45 exons changes during thymocyte selection.

Induction of autoimmunity in the absence of CD28 costimulation.

Ag-specific activation of T lymphocytes requires two signals, one by the TCR and a second by costimulatory molecules. In a CD4+ T helper cell-dependent experimental autoimmune myocarditis model, we provide genetic evidence that cardiac myosin-induced autoimmune myocarditis and the production of IgG auto-Abs is dependent on functional T cells and did not occur in mice lacking the tyrosine kinase p56lck or the tyrosine phosphatase CD45. By contrast, animals lacking the T cell-costimulatory molecule CD28 (CD28 -/-) developed autoimmune heart disease, although at significantly lower severity than in heterozygous littermates, and produced IgG auto-Abs depending on the concentration of the autoantigen administered.

Alloreactive gamma delta thymocytes utilize distinct costimulatory signals from peripheral T cells.

Interactions between CD28/CTLA-4 on T cells and CD80 (B7.1) and CD86 (B7.2) counter receptors provide crucial costimulatory signals for TCR-alpha beta+ lymphocytes.