Lipids from Mycobacterium leprae cell wall suppress T-cell activation in vivo and in vitro

The influence of Mycobacterium leprae cell wall lipids on lymphocyte functions has been investigated in vivo (delayed-type hypersensitivity) and in vitro. The inflammatory response has been earlier evaluated by the mouse footpad oedema model and the delipidated mycobacteria evoked a mild but significant inflammatory response. Herein a higher level of hypersensitivity reaction was observed with delipidated bacilli than with the intact mycobacteria. The lipids obtained from the extract of M. leprae external cell wall were used to prepare liposomes, which have not been shown to be toxic to lymphocytes. The method of lipidic extraction and the sodium dodecyl sulphate-polyacrylamide gel electrophoresis of the lipid fraction did not reveal any trace of proteins. Thin-layer chromatography of this extract detected four different bands with an apolar character, suggestive of mycolic and fatty acids. These same M. leprae liposomes potently suppressed lymph node cells, as well CD4+ and CD8+ T-cell lines, and an antigen-specific T-cell clone (T 4-9) proliferation, even under potent stimulus. Cholesterol-choline liposomes, unrelated to M. leprae liposomes, used as a control in the biological assays showed no significant effect on lymphoblastic activity, which points to the specificity of M. leprae lipids. These data demonstrated that M. leprae cell wall lipids induce immune suppression in mice without causing any membrane alteration in T cells as assessed throughout kinetic studies in vitro. This fact is closely related to the down-regulating effect induced by M. leprae lipids which we have previously observed in macrophage functions in vivo and in vitro. Although this lipidic fraction showed a suppressive action on T lymphocytes in vitro (proliferation) and in vivo (delayed-type hypersensitivity), its possible significance in the establishment of a specific immune response to M. leprae must be further investigated.