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Phenotypic and Functional Analysis of Activated Regulatory T Cells Isolated from Chronic Lymphocytic Choriomeningitis Virus-infected Mice
Published on: June 22, 2016
Alterations in early biochemical events following T cell activation in leprosy patients
N Sharma1, V K Sharma, A Gupta
1Department of Dermatology, Venerology, and Leprology, Postgraduate Institute of Medical Education and Research, Chandigarh, 160012, India.
Insights
Leprosy patients
Area of Science:
- Immunology
- Infectious Diseases
- Cellular Biology
Background:
- Leprosy presents diverse clinical forms, paucibacillary (TT/BT) and multibacillary (BL/LL), with distinct immune responses.
- Understanding early lymphocyte activation and cytokine profiles is crucial for elucidating disease pathogenesis in leprosy.
Purpose of the Study:
- To investigate early lymphocyte activation events and cytokine profiles (IL-2, IL-4, IL-6) in paucibacillary and multibacillary leprosy.
- To assess the role of Mycobacterium leprae antigen (PGL-1) in modulating immune responses in different leprosy forms.
Main Methods:
- Lymphocyte stimulation using phorbol myristate acetate/A23187 (PMA/A23187) and Mycobacterium leprae antigen (PGL-1).
- Measurement of intracellular signaling molecules (IP3, calcium, protein kinase C) and cytokine levels (IL-2, IL-4, IL-6).
- Comparative analysis between lymphocytes from TT/BT and BL/LL leprosy patients.
Main Results:
- Lymphocytes from TT/BT patients exhibited greater proliferation to PMA/A23187 and PGL-1 compared to BL/LL.
- Early activation markers (IP3, calcium, PKC) were elevated in both groups, with a significant increase in TT/BT post-PMA/A23187 stimulation.
- PGL-1 marginally increased IP3 in TT/BT but had no effect in BL/LL. IL-2 was enhanced in TT/BT, while IL-4 and IL-6 were increased in BL/LL, further augmented by PGL-1.
Conclusions:
- PGL-1 appears to be a key factor in driving the T-helper 2 (TH2) cytokine response characteristic of lepromatous leprosy (BL/LL).
- Differential lymphocyte activation and cytokine profiles correlate with the clinical spectrum of leprosy, highlighting distinct immune responses.
Abstract:
The early events of activation and cytokine profiles (IL-2, 4, and 6) were studied in lymphocytes of paucibacillary (TT/BT) and multibacillary (BL/LL) leprosy patients after stimulation with PMA/A23187 and Mycobacterium leprae antigen (PGL-1). Lymphocytes from BT/TT patients showed proliferation in response to both PMA/A23187 and PGL-1 compared to BL/LL. The levels of early activation signaling molecules such as IP3, calcium, and protein kinase C (PKC) in the particulate fraction were found to be elevated in BT/TT and BL/LL patients and showed a further significant increase after stimulation with PMA/A23187 in BT/TT patients. PGL-1 marginally increased the IP3 levels in BT/TT patients, whereas in BL/LL patients, it had no effect. The levels of IL-2 were enhanced in lymphocytes of BT/TT leprosy patients and were further augmented by PPD and PGL-1, while the levels of IL-4 and IL-6 were increased in LL/BL lymphocytes and further augmented by PGL-1. Thus PGL-1 seems to be a major culprit in inducing the TH2-type cytokine response observed in lepromatous leprosy patients.
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