Leprosy, a debilitating disease shows manifestations ranging from strong cell mediated immune (CMI) response in tuberculoid form (BT/TT) or weak CMI with immunological anergy in lepromatous form (BULL). Repeated stimulation with mycobacterial antigen causes activation induced cell death (apoptosis) or anergy in these patients. Previous studies showed in vitro T cell proliferation and increased Th1 response with liposomal (particulate) presentation of mycobacterial antigens with immunomodulators (MDP analog, murabutide and T cell peptide of Trat protein). In the present study, the role of caspases; expression of apoptotic markers, CD95 and CD95L in T cells of leprosy patients and the effect of particulate formulations in the reversal of apoptosis in BUTT and BULL patient group was studied. Caspase 8/3 activity was maximum (p < 0.01) in BULL patients in constitutive state, which was followed by decreased activity in BT/TT and normal subjects. Caspase 8/3 activity increased significantly (p < 0.05) from constitutive state after 5 days of antigen stimulation (inducible state). Both the antigens were equally potent in inducing the apoptosis in leprosy patients. A decreased caspase activity using the particulate formulations of both antigens was observed in BULL group. The expression of CD95 and CD95L in T cells of leprosy patients increased significantly after 5 days of antigen stimulation. However, % expression of apoptotic markers by T cells of BULL patients decreased significantly (P < 0.05) when the particulate formulations were used. To summarize, the particulate formulations of antigens with immunomodulators slowed down the apoptosis and hence T cell anergy in leprosy by stimulating the cells to proliferate. (C) 2004 Elsevier B.V. All rights reserved.