T-cell regulation in lepromatous leprosy.
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.
The Dept. of Infectious Diseases, Leiden University Medical Center, Leiden, The Netherlands; Armauer Hansen Research Institute and ALERT hospital, Addis Ababa, Ethiopia.
Kidist
K
Bobosha
The Dept. of Infectious Diseases, Leiden University Medical Center, Leiden, The Netherlands.
Louis
L
Wilson
The Dept. of Infectious Diseases, Leiden University Medical Center, Leiden, The Netherlands.
Krista E
KE
van Meijgaarden
Armauer Hansen Research Institute and ALERT hospital, Addis Ababa, Ethiopia.
Yonas
Y
Bekele
Armauer Hansen Research Institute and ALERT hospital, Addis Ababa, Ethiopia.
Martha
M
Zewdie
The Dept. of Infectious Diseases, Leiden University Medical Center, Leiden, The Netherlands.
Jolien J
JJ
van der Ploeg-van Schip
Armauer Hansen Research Institute and ALERT hospital, Addis Ababa, Ethiopia.
Markos
M
Abebe
Armauer Hansen Research Institute and ALERT hospital, Addis Ababa, Ethiopia.
Jemal
J
Hussein
Mycobacterial Research Laboratory, Anandaban Hospital, Kathmandu, Nepal.
Saraswoti
S
Khadge
Mycobacterial Research Laboratory, Anandaban Hospital, Kathmandu, Nepal.
Kapil D
KD
Neupane
Mycobacterial Research Laboratory, Anandaban Hospital, Kathmandu, Nepal.
Deanna A
DA
Hagge
The Dept. of Obstetrics and Gynaecology, Free University Amsterdam, Center for Gynaecologic Oncology, Amsterdam, The Netherlands.
Ekaterina S
ES
Jordanova
Armauer Hansen Research Institute and ALERT hospital, Addis Ababa, Ethiopia.
Abraham
A
Aseffa
The Dept. of Infectious Diseases, Leiden University Medical Center, Leiden, The Netherlands.
Tom H M
TH
Ottenhoff
The Dept. of Infectious Diseases, Leiden University Medical Center, Leiden, The Netherlands.
Annemieke
A
Geluk
D001706:Biopsy; D006801:Humans; D007150:Immunohistochemistry; D016130:Immunophenotyping; D007371:Interferon-gamma / Q000378:metabolism; D015440:Leprosy, Lepromatous / Q000276:immunology*; D007963:Leukocytes, Mononuclear / Q000276:immunology; D018613:Microscopy, Confocal; D009166:Mycobacterium leprae / Q000276:immunology*; D012867:Skin / Q000473:pathology; D016176:T-Lymphocyte Subsets / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*
D007371:Interferon-gamma