| Autor: |
Bobosha K; The Dept. of Infectious Diseases, Leiden University Medical Center, Leiden, The Netherlands; Armauer Hansen Research Institute and ALERT hospital, Addis Ababa, Ethiopia., Wilson L; The Dept. of Infectious Diseases, Leiden University Medical Center, Leiden, The Netherlands., van Meijgaarden KE; The Dept. of Infectious Diseases, Leiden University Medical Center, Leiden, The Netherlands., Bekele Y; Armauer Hansen Research Institute and ALERT hospital, Addis Ababa, Ethiopia., Zewdie M; Armauer Hansen Research Institute and ALERT hospital, Addis Ababa, Ethiopia., van der Ploeg-van Schip JJ; The Dept. of Infectious Diseases, Leiden University Medical Center, Leiden, The Netherlands., Abebe M; Armauer Hansen Research Institute and ALERT hospital, Addis Ababa, Ethiopia., Hussein J; Armauer Hansen Research Institute and ALERT hospital, Addis Ababa, Ethiopia., Khadge S; Mycobacterial Research Laboratory, Anandaban Hospital, Kathmandu, Nepal., Neupane KD; Mycobacterial Research Laboratory, Anandaban Hospital, Kathmandu, Nepal., Hagge DA; Mycobacterial Research Laboratory, Anandaban Hospital, Kathmandu, Nepal., Jordanova ES; The Dept. of Obstetrics and Gynaecology, Free University Amsterdam, Center for Gynaecologic Oncology, Amsterdam, The Netherlands., Aseffa A; Armauer Hansen Research Institute and ALERT hospital, Addis Ababa, Ethiopia., Ottenhoff TH; The Dept. of Infectious Diseases, Leiden University Medical Center, Leiden, The Netherlands., Geluk A; The Dept. of Infectious Diseases, Leiden University Medical Center, Leiden, The Netherlands. |
| Abstrakt: |
Regulatory T (Treg) 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+ Treg cells play a role in M. leprae-Th1 unresponsiveness in LL. |
