T-Cell Regulation in Lepromatous Leprosy

Regulatory T (T(reg)) cells are known for their role in maintaining self-tolerance and balancing immune reactions in autoimmune diseases and chronic infections. However, regulatory mechanisms can also lead to prolonged survival of pathogens in chronic infections like leprosy and tuberculosis (TB). Despite high humoral responses against Mycobacterium leprae (M. leprae), lepromatous leprosy (LL) patients have the characteristic inability to generate T helper 1 (Th1) responses against the bacterium. In this study, we investigated the unresponsiveness to M. leprae in peripheral blood mononuclear cells (PBMC) of LL patients by analysis of IFN-γ responses to M. leprae before and after depletion of CD25(+) cells, by cell subsets analysis of PBMC and by immunohistochemistry of patients' skin lesions. Depletion of CD25(+) cells from total PBMC identified two groups of LL patients: 7/18 (38.8%) gained in vitro responsiveness towards M. leprae after depletion of CD25(+) cells, which was reversed to M. leprae-specific T-cell unresponsiveness by addition of autologous CD25(+) cells. In contrast, 11/18 (61.1%) remained anergic in the absence of CD25(+) T-cells. For both groups mitogen-induced IFN-γ was, however, not affected by depletion of CD25(+) cells. In M. leprae responding healthy controls, treated lepromatous leprosy (LL) and borderline tuberculoid leprosy (BT) patients, depletion of CD25(+) cells only slightly increased the IFN-γ response. Furthermore, cell subset analysis showed significantly higher (p = 0.02) numbers of FoxP3(+) CD8(+)CD25(+) T-cells in LL compared to BT patients, whereas confocal microscopy of skin biopsies revealed increased numbers of CD68(+)CD163(+) as well as FoxP3(+) cells in lesions of LL compared to tuberculoid and borderline tuberculoid leprosy (TT/BT) lesions. Thus, these data show that CD25(+) T(reg) cells play a role in M. leprae-Th1 unresponsiveness in LL

The Effect of Hyperglycaemia on In Vitro Cytokine Production and Macrophage Infection with Mycobacterium tuberculosis

Immunogenetics and cellular immunology of bacterial infectious disease

Examination of the genetic factors underlying the cognitive variability associated with neurofibromatosis type 1

PURPOSE: Neurofibromatosis type 1 (NF1) is an autosomal dominant disorder associated with cognitive deficits. The NF1 cognitive phenotype is generally considered to be highly variable, possibly due to the observed T2-weighted hyperintensities, loss of heterozygosity, NF1-specific genetic modifiers, or allelic imbalance. METHODS: We investigated cognitive variability and assessed the contribution of genetic factors by performing a retrospective cohort study and a monozygotic twin case series. We included data of 497 children with genetically confirmed NF1 and an IQ assessment, including 12 monozygotic twin and 17 sibling sets. RESULTS: Individuals carrying an NF1 chromosomal microdeletion showed significant lower full-scale IQ (FSIQ) scores than individuals carrying intragenic pathogenic NF1 variants. For the intragenic subgroup, the variability in cognitive ability and the correlation of IQ between monozygotic NF1 twin pairs or between NF1 siblings is similar to the general population. CONCLUSIONS: The variance and heritability of IQ in individuals with NF1 are similar to that of the general population, and hence mostly driven by genetic background differences. The only factor that significantly attenuates IQ in NF1 individuals is the NF1 chromosomal microdeletion genotype. Implications for clinical management are that individuals with intragenic NF1 variants that score <1.5-2 SD below the mean of the NF1 population should be screened for additional causes of cognitive disability.status: publishe

A study on synaptic coupling between single orofacial mechanoreceptors and human masseter muscle

The original publication can be found at www.springerlink.comThe connection between individual orofacial mechanoreceptive afferents and the motoneurones that innervate jaw muscles is not well established. For example, although electrical and mechanical stimulation of orofacial afferents in bulk evokes responses in the jaw closers, whether similar responses can be evoked in the jaw muscles from the discharge of type identified single orofacial mechanoreceptive afferents is not known. Using tungsten microelectrodes, we have recorded from 28 afferents in the inferior alveolar nerve and 21 afferents in the lingual nerve of human volunteers. We have used discharges of single orofacial afferents as the triggers and the electromyogram (EMG) of the masseter as the source to generate spike-triggered averaged records to illustrate time-based EMG modulation by the nerve discharge. We have then used cross correlation analysis to quantify the coupling. Furthermore, we have also used coherence analysis to study frequency-based relationship between the nerve spike trains and the EMG. The discharge patterns of the skin and mucosa receptors around the lip and the gingiva generated significant modulation in EMGs with a success rate of 40% for both cross correlation and coherence analyses. The discharge patterns of the periodontal mechanoreceptors (PMRs) generated more coupling with a success rate of 70% for cross correlation and about 35% for coherence analyses. Finally, the discharges of the tongue receptors displayed significant coupling with the jaw muscle motoneurones with a success rate of about 40% for both analyses. Significant modulation of the jaw muscles by single orofacial receptors suggests that they play important roles in controlling the jaw muscle activity so that mastication and speech functions are executed successfully.Kemal S. Türker, Skjalg E. Johnsen, Paul F. Sowman and Mats Trulsso