Inhibition of apoptosis, activation of NKT cell and upregulation of CD40 and CD40L mediated by M. leprae antigen(s) combined with Murabutide and Trat peptide in leprosy patients |
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Authors: | Vineeta Chattree Neena Khanna Vandana Bisht D N Rao |
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Institution: | (1) Department of Biochemistry, All India Institute of Medical Sciences, Ansari Nagar, New Delhi, 110029, India;(2) Department of Dermatovenereology, All India Institute of Medical Sciences, Ansari Nagar, New Delhi, India |
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Abstract: | Protective immunity against intracellular pathogen Mycobacterium leprae is dependent on the activation of T cells. Repeated stimulation of T cells by M. leprae antigens MLCwA (M. leprae total cell wall antigen) and ManLAM (mannose-capped lipoarabinomannan), may lead to apoptosis in leprosy patients. In the
present study, inhibition of the Fas-induced apoptosis of peripheral blood mononuclear cells of leprosy patients was investigated
using above M. leprae antigen(s), in combination with immunomodulators murabutide (MB) and a Trat peptide in particulate form (liposome). Incubation
of the cells with antigen containing the two immunomodulators in particulate form (liposomes) led to decrease in percentage
of propidium iodide positive cells and T cells expressing Fas–FasL as well as decreased caspase-8/-3 activities in lepromatous
patients, thereby inhibiting apoptosis, while converse was true upon stimulation with soluble antigen. Concurrently, there
was an upregulation of antiapoptotic protein Bcl-xL in lepromatous patients, leading to the inhibition of apoptosis. It was also observed that same formulation upregulated the
expression of CD40 on B cells and monocytes-macrophages and CD40L on T cells of lepromatous leprosy patients. The same liposomal
formulation significantly increased the expression of CD1b and CD1d on monocytes-macrophages as well as percentage of NKT
cells secreting IFN-γ in lepromatous leprosy patients. Thus, the liposomal formulation of antigen with the immunomodulators
in vitro promoted the activation of CD40:CD40L pathways and NKT cell function involved in providing cell-mediated immunity
to these patients. The same formulation also caused reversal of T cell anergy by inhibiting apoptosis through decreased expression
of death receptors (Fas–FasL) and caspase activities (3 and 8) and increased expression of antiapoptotic protein Bcl-xL in these patients. |
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Keywords: | M leprae antigen Apoptosis Fas– FasL CD40– CD40L Natural killer T cells Liposomes Immunomodulators |
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