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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
medicine
T-Cell Regulation in Lepromatous Leprosy
PLoS Neglected Tropical Diseases, Volume 8, No. 4, Article e2773, Year 2014
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Description
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. © 2014 Bobosha et al.
Available Materials
https://efashare.b-cdn.net/share/pmc/articles/PMC3983090/bin/pntd.0002773.s001.tif
https://efashare.b-cdn.net/share/pmc/articles/PMC3983090/bin/pntd.0002773.s002.tif
https://efashare.b-cdn.net/share/pmc/articles/PMC3983090/bin/pntd.0002773.s003.tif
Authors & Co-Authors
Bobosha, Kidist
Netherlands, Leiden
Leids Universitair Medisch Centrum
Ethiopia, Addis Ababa
Armauer Hansen Research Institute
Wilson, Louis G.
Netherlands, Leiden
Leids Universitair Medisch Centrum
van Meijgaarden, Krista E.
Netherlands, Leiden
Leids Universitair Medisch Centrum
Bekele, Yonas Y.
Ethiopia, Addis Ababa
Armauer Hansen Research Institute
Zewdie, Martha
Ethiopia, Addis Ababa
Armauer Hansen Research Institute
van der Ploeg-van Schip, Jolien J.
Netherlands, Leiden
Leids Universitair Medisch Centrum
Abebe, Markos
Ethiopia, Addis Ababa
Armauer Hansen Research Institute
Hussein, Jemal
Ethiopia, Addis Ababa
Armauer Hansen Research Institute
Khadge, Saraswoti
Nepal, Kathmandu
Anandaban Leprosy Hospital
Neupane, Kapil Dev
Nepal, Kathmandu
Anandaban Leprosy Hospital
Hagge, Deanna Alisa
Nepal, Kathmandu
Anandaban Leprosy Hospital
Jordanova, Ekaterina S.
Netherlands, Amsterdam
Vrije Universiteit Amsterdam
Aseffa, Abraham
Ethiopia, Addis Ababa
Armauer Hansen Research Institute
Ottenhoff, Tom H.M.
Netherlands, Leiden
Leids Universitair Medisch Centrum
Geluk, Annemieke
Netherlands, Leiden
Leids Universitair Medisch Centrum
Statistics
Citations: 73
Authors: 15
Affiliations: 4
Identifiers
Doi:
10.1371/journal.pntd.0002773
ISSN:
19352727
e-ISSN:
19352735
Research Areas
Infectious Diseases