Differential development of CD4 and CD8 cytotoxic T cells (CTL) in PBMC across the leprosy spectrum; IL-6 with IFN-gamma or IL-2 generate CTL in multibacillary patients.

In the present study we evaluated the contribution of CD4 and CD8 T cells on the antigen-specific cytotoxic activity induced by whole Mycobacterium leprae in leprosy patients and normal controls (N) as well as the modulation of this activity by some cytokines. Peripheral blood mononuclear cells (PBMC) from N or from leprosy patients were stimulated with antigen in the presence or absence of cytokines for 7 days. M. leprae-stimulated PBMC were depleted of CD4 or CD8 antigen-bearing cells and employed as effector cells in a 4-hr [31Cr]-release assay against autologous M. leprae-pulsed macrophages. Our results demonstrate that both CD4 and CD8 T cells contribute to M. leprae-induced cytotoxic activity, with differences observed in paucibacillary (PB) and multibacillary (MB) patients. CD8-mediated cytotoxic activity is higher than that of CD4 cells in PB patients, while in MB patients CD4 cytotoxicity is predominant. Our data also demonstrate that the generation of CD4 and CD8 cytotoxic T lymphocytes (CTL) can be modulated differentially by interleukin-4 (IL-4), IL-6, gamma interferon (IFN-gamma), or IL-2. Although MB patients developed the lowest CTL response, cytokines such as IL-6 plus IL-2 or IFN-gamma were able to generate both CD4 and CD8 cytotoxic T cells from MB patients. In PB patients, IL-6 plus IFN-gamma displayed the highest stimulation on CD8 effector cells. Thus, an important role may be assigned to IL-6, together with IL-2 or IFN-gamma, in the differentiation of M. leprae-specific CTL effector cells.