03065nas a2200433   4500000000100000008004100001260001300042653003800055653001000093653002400103653001700127653001400144653001800158653001600176653001400192653001400206653001400220653001100234653001100245653002400256653002600280653001200306653002600318653000900344653001600353653002500369653001400394653001800408653001800426100001500444700001300459700001200472700001200484245018300496300001000679490000800689520192000697022001402617       2008                            d  c2008 Feb10aAcetylmuramyl-Alanyl-Isoglutamine10aAdult10aAntigens, Bacterial10aAntigens, CD10aApoptosis10aCD40 Antigens10aCD40 Ligand10aCaspase 310aCaspase 810aCytokines10aFemale10aHumans10aImmunologic Factors10aKiller Cells, Natural10aleprosy10aLymphocyte Activation10aMale10aMiddle Aged10aMycobacterium leprae10aPropidium10aUp-Regulation10aBcl-X Protein1 aChattree V1 aKhanna N1 aBisht V1 aRao D N00aInhibition 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.  a87-970 v3093 a<p>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.</p>  a0300-8177