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Immunological defect in leprosy patients: altered T-lymphocyte signals
N Sharma1, V K Sharma, A Gupta
1Department of Dermatology, Venereology and Leprology, Postgraduate Institute of Medical Education and Research, Chandigarh, India.
Insights
T-lymphocyte activation differs between leprosy types. Paucibacillary (TT/BT) patients show heightened responses to mitogens and antigens, unlike multibacillary (BL/LL) patients who exhibit anergic cells due to altered signal transduction.
Area of Science:
- Immunology
- Cellular Biology
Background:
- Leprosy classification (TT/BT and BL/LL) reflects distinct immune responses.
- Understanding T-lymphocyte activation is crucial for leprosy pathogenesis.
Purpose of the Study:
- To investigate early T-lymphocyte activation events in different leprosy forms.
- To correlate signal transduction pathways with immune status in leprosy patients.
Main Methods:
- Lymphocyte stimulation using mitogenic agents (calcium ionophore A23187/PMA) and Mycobacterium leprae antigen (PGL-1).
- Measurement of inositol triphosphate (IP3) and intracellular calcium ([Ca2+]i) levels.
- Assessment of Protein Kinase C (PKC) translocation.
Main Results:
- BT/TT patients and controls showed maximum proliferation to PMA/A23187 and PGL-1, respectively.
- Elevated IP3 and [Ca2+]i were constitutive in BT/TT and BL/LL patients.
- T-lymphocytes in BT/TT patients were preactivated and responsive, while BL/LL patient cells were unresponsive to PGL-1.
Conclusions:
- Altered signal transduction events in multibacillary leprosy correlate with T-cell anergy.
- Distinct T-lymphocyte activation patterns differentiate leprosy subtypes.
Abstract:
The early events of activation were studied in paucibacillary (TT/BT) and multibacillary (BL/LL) leprosy patients by stimulation of their lymphocytes with mitogenic agents (calcium ionophore A23187/PMA) and Micobacterium leprae antigen (PGL-1). Maximum proliferation in response to PMA/A23187 and PGL-1 was observed in the BT/TT patients and the control group, respectively. Inositol triphosphate (IP3) and calcium were constitutively elevated in BT/TT and LL/BL patients. PMA/A23187 caused an increase in both IP3 and [Ca2+]i in BT/TT patients and controls. PGL-1 marginally increased IP3 levels in BT/TT patients. In the LL/BL patients, although PMA/A23187 increased IP3 levels, but no change was seen in [Ca2+]i, PGL-1 had no effect. Protein kinase C levels were seen to be associated with particulate fractions in BT/TT patients and were found to increase further in response to PMA/A23187. PGL-1 did not increase translocation of protein kinase C in controls or LL/BL patients. A preactivated and sensitised state of T-lymphocytes was observed in BT/TT patients, responsive to antigen and mitogens, whereas the cells of LL/BL patients were unresponsive to PGL-1. The altered signal transduction events characterised in the MB patients thus correlate well with the anergic state of their cells.