RESUMEN
The present study evaluates role of Notch1 signaling in the regulation of T cell immunity in leprosy. Peripheral blood mononuclear cells from leprosy patients and healthy controls were activated with Mycobacterium leprae antigens along with activation of Notch1 signaling pathway and then lymphoproliferation was analyzed by lymphocytes transformation test and the expression of Notch1 and its ligands DLL1, Jagged1 and Jagged 2, T cell activation marker and Th1-Th2 cytokines on Th cells in PBMCs of study subjects were analyzed by flow cytometry. Further, these parameters were also analyzed after inhibition of Notch1 signaling pathway. Higher percentage of Notch1expressing Th cells were noted in TT/BT cases and higher percentage of DLL1 expressing Th cells in TT/BT and BL/LL cases. M. leprae antigens were found to induce the expression of Jagged1 on Th cells. Interestingly activation of Notch1 signaling pathway induced lymphoproliferation in BL/LL cases in response of PGL-1. Activation of Notch1 signaling was also found to induce the expression of T cell activation markers CD25, CD69 and Th1 cytokine IFN-γ in response to M. leprae antigens. Immunomodulation through Notch1 signaling seen in our study could be helpful in augmenting Th1 response in leprosy.
Asunto(s)
Antígenos Bacterianos/inmunología , Glucolípidos/inmunología , Lepra/inmunología , Mycobacterium leprae/inmunología , Receptor Notch1/metabolismo , Células TH1/inmunología , Células Th2/inmunología , Antígenos CD/metabolismo , Antígenos de Diferenciación de Linfocitos T/metabolismo , Proteínas de Unión al Calcio/genética , Proteínas de Unión al Calcio/metabolismo , Diferenciación Celular , Proliferación Celular , Células Cultivadas , Progresión de la Enfermedad , Citometría de Flujo , Humanos , Inmunomodulación , Interferón gamma/metabolismo , Proteína Jagged-1/genética , Proteína Jagged-1/metabolismo , Lectinas Tipo C/metabolismo , Activación de Linfocitos , Proteínas de la Membrana/genética , Proteínas de la Membrana/metabolismo , Transducción de Señal , Balance Th1 - Th2RESUMEN
Comparisons of the structures of different mouse MHC class I molecules define how polymorphic residues determine the unique structural motif and atomic anchoring of their bound peptides. Here, Ted Hansen and colleagues speculate that quantitative differences in how class I molecules interact with peptide, beta2-microglobulin and molecular chaperones that facilitate peptide loading might determine their relative participation in different pathways of antigen presentation.