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-gamma 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.