Impaired Thymic Selection and Abnormal Antigen-Specific T Cell Responses in Foxn1Δ/Δ Mutant Mice

Foxn1(Δ/Δ) mutant mice have a specific defect in thymic development, characterized by a block in TEC differentiation at an intermediate progenitor stage, and blocks in thymocyte development at both the DN1 and DP cell stages, resulting in the production of abnormally functioning T cells that develop from an atypical progenitor population. In the current study, we tested the effects of these defects on thymic selection.We used Foxn1(Δ/Δ); DO11 Tg and Foxn1(Δ/Δ); OT1 Tg mice as positive selection and Foxn1(Δ/Δ); MHCII I-E mice as negative selection models. We also used an in vivo system of antigen-specific reactivity to test the function of peripheral T cells. Our data show that the capacity for positive and negative selection of both CD4 and CD8 SP thymocytes was reduced in Foxn1(Δ/Δ) mutants compared to Foxn1(+/Δ) control mice. These defects were associated with reduction of both MHC Class I and Class II expression, although the resulting peripheral T cells have a broad TCR Vβ repertoire. In this deficient thymic environment, immature CD4 and CD8 SP thymocytes emigrate from the thymus into the periphery. These T cells had an incompletely activated profile under stimulation of the TCR signal in vitro, and were either hypersensitive or hyporesponsive to antigen-specific stimulation in vivo. These cell-autonomous defects were compounded by the hypocellular peripheral environment caused by low thymic output.These data show that a primary defect in the thymic microenvironment can cause both direct defects in selection which can in turn cause indirect effects on the periphery, exacerbating functional defects in T cells

Heme oxygenase-1 and carbon monoxide in pulmonary medicine

Heme oxygenase-1 (HO-1), an inducible stress protein, confers cytoprotection against oxidative stress in vitro and in vivo. In addition to its physiological role in heme degradation, HO-1 may influence a number of cellular processes, including growth, inflammation, and apoptosis. By virtue of anti-inflammatory effects, HO-1 limits tissue damage in response to proinflammatory stimuli and prevents allograft rejection after transplantation. The transcriptional upregulation of HO-1 responds to many agents, such as hypoxia, bacterial lipopolysaccharide, and reactive oxygen/nitrogen species. HO-1 and its constitutively expressed isozyme, heme oxygenase-2, catalyze the rate-limiting step in the conversion of heme to its metabolites, bilirubin IXα, ferrous iron, and carbon monoxide (CO). The mechanisms by which HO-1 provides protection most likely involve its enzymatic reaction products. Remarkably, administration of CO at low concentrations can substitute for HO-1 with respect to anti-inflammatory and anti-apoptotic effects, suggesting a role for CO as a key mediator of HO-1 function. Chronic, low-level, exogenous exposure to CO from cigarette smoking contributes to the importance of CO in pulmonary medicine. The implications of the HO-1/CO system in pulmonary diseases will be discussed in this review, with an emphasis on inflammatory states

Effects of different drying temperatures on the physical and mechanical properties of some marbles (Muğla, Turkey) during salt crystallization tests

This study aims to understand the effects of drying temperatures during sodium sulphate salt crystallization tests on the physico-mechanical properties of some Mug. la marbles. Four commercially available and extensively used Turkish marbles, namely Mug. la white, Milas white, Derebag white and Milas Pearl, having different textural properties were subjected to sodium sulphate salt crystallization tests with 30, 60 and 100 degrees C drying temperatures. The change in the physico-mechanical properties of the marbles including weight, dry and saturated unit weights, water absorption, effective porosity, dry and saturated sonic velocities and dry uniaxial compressive strength has been determined for various stages of the salt crystallization tests. The results were evaluated in terms of drying temperatures and the textural properties of the marbles. Based on the test results, the salt crystallization with the drying temperature of 100 degrees C causes significant damage to all marbles. However, the drying temperature of the test at 60 degrees C gives rise to moderate damage, whereas the drying of the marbles at 30 degrees C gives the least damage. Therefore, the drying temperature of the salt crystallization tests should be less than 60 degrees C and preferably around 30 degrees C in order to avoid additional thermal effects on marbles. Furthermore, the fine-gained Milas pearl marble with irregular grain boundary is found to be the most resistant one against the salt crystallization