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Published on: March 23, 2014
Assessment of cell mediated immunogenicity of Mycobacterium leprae-derived antigens
Yumi Maeda1, Masaichi Gidoh, Norihisa Ishii
1Department of Microbiology, Leprosy Research Center, National Institute of Infectious Diseases, 4-2-1 Aoba-cho, Higashimurayama, 189-0002, Tokyo, Japan.
Insights
Mycobacterium leprae cell membrane antigens stimulate human dendritic cells, enhancing T cell responses. These M. leprae membrane antigens show potential as effective leprosy vaccine candidates.
Area of Science:
- Immunology
- Microbiology
- Vaccinology
Background:
- Leprosy remains a significant global health challenge.
- Understanding the immune response to Mycobacterium leprae is crucial for vaccine development.
Purpose of the Study:
- To investigate the antigenicity of Mycobacterium leprae (M. leprae) cell membrane fraction.
- To evaluate the potential of M. leprae membrane antigens as vaccine candidates.
Main Methods:
- Human dendritic cells (DCs) were exposed to M. leprae cell membrane fraction.
- DC maturation markers (MHC class II, CD86, CD83) and cytokine production (IL-12 p70) were assessed.
- T cell responses (IFN-gamma, perforin) were measured following co-culture with stimulated DCs.
Main Results:
- M. leprae membrane components were internalized by DCs, leading to antigen presentation.
- DCs stimulated with membrane antigens showed upregulated expression of maturation markers and IL-12 p70.
- Stimulated DCs induced significantly higher interferon-gamma (IFN-gamma) production in both CD4+ and CD8+ T cells compared to live M. leprae or cytosol fractions.
- T cells from leprosy patients exhibited enhanced IFN-gamma production.
- Intracellular perforin production in CD8+ T cells increased in an antigen-dose dependent manner.
Conclusions:
- M. leprae membrane antigens effectively stimulate dendritic cells and T cell immunity.
- These findings suggest M. leprae membrane antigens hold promise as vaccine agents against leprosy.
Abstract:
The antigenicity of Mycobacterium leprae (M. leprae)-derived cell membrane fraction was examined using human dendritic cells (DCs). Immature DCs internalized and processed the cell membrane components, and expressed M. leprae-derived antigens (Ags) on their surface. The expression of MHC class II, CD86, and CD83 Ags on DCs and CD40 ligand (L)-associated IL-12 p70 production from DCs were up-regulated by the membrane Ags. Moreover these stimulated DCs induced significantly higher level of interferon-gamma (IFN-gamma) production by autologous CD4(+) and CD8(+) T cells than those pulsed with equivalent doses of live M. leprae or its cytosol fraction. Both subsets of T cells from tuberculoid leprosy patients also produced several fold more IFN-gamma than those from normal individuals. Furthermore, the intracellular perforin production in CD8(+) T cells was up-regulated in an Ag-dose dependent manner. These results suggest that M. leprae membrane Ags might be useful as the vaccinating agents against leprosy.
