Leprosy is a chronic disease caused by infection that can cause severe neurological complications and physical disabilities. A leprosy-specific vaccine would be an important component within control programs but is still lacking. Given that multifunctional CD4 T cells [i.e., those capable of simultaneously secreting combinations of interferon (IFN)-γ, interleukin (IL)-2, and tumor necrosis factor (TNF)] have now been implicated in the protective response to several infections, we tested the hypothesis if a recombinant antigen-specific multifunctional T cells differed between leprosy patients and their healthy contacts. We used whole blood assays and peripheral blood mononuclear cells to characterize the antigen-specific T cell responses of 39 paucibacillary (PB) and 17 multibacillary (MB) leprosy patients and 31 healthy household contacts (HHC). Cells were incubated with either crude mycobacterial extracts ( cell sonicate-MLCS) and purified protein derivative (PPD) or recombinant ML2028 protein, the homolog of Ag85B. Multiplex assay revealed antigen-specific production of IFN-γ and IL-2 from cells of HHC and PB, confirming a Th1 bias within these individuals. Multiparameter flow cytometry then revealed that the population of multifunctional ML2028-specific T cells observed in HHC was larger than that observed in PB patients. Taken together, our data suggest that these multifunctional antigen-specific T cells provide a more effective response against infection that prevents the development of leprosy. These data further our understanding of infection/leprosy and are instructive for vaccine development.
BT - Frontiers in immunology C1 -http://www.ncbi.nlm.nih.gov/pubmed/30631322?dopt=Abstract
DO - 10.3389/fimmu.2018.02920 J2 - Front Immunol LA - eng N2 -Leprosy is a chronic disease caused by infection that can cause severe neurological complications and physical disabilities. A leprosy-specific vaccine would be an important component within control programs but is still lacking. Given that multifunctional CD4 T cells [i.e., those capable of simultaneously secreting combinations of interferon (IFN)-γ, interleukin (IL)-2, and tumor necrosis factor (TNF)] have now been implicated in the protective response to several infections, we tested the hypothesis if a recombinant antigen-specific multifunctional T cells differed between leprosy patients and their healthy contacts. We used whole blood assays and peripheral blood mononuclear cells to characterize the antigen-specific T cell responses of 39 paucibacillary (PB) and 17 multibacillary (MB) leprosy patients and 31 healthy household contacts (HHC). Cells were incubated with either crude mycobacterial extracts ( cell sonicate-MLCS) and purified protein derivative (PPD) or recombinant ML2028 protein, the homolog of Ag85B. Multiplex assay revealed antigen-specific production of IFN-γ and IL-2 from cells of HHC and PB, confirming a Th1 bias within these individuals. Multiparameter flow cytometry then revealed that the population of multifunctional ML2028-specific T cells observed in HHC was larger than that observed in PB patients. Taken together, our data suggest that these multifunctional antigen-specific T cells provide a more effective response against infection that prevents the development of leprosy. These data further our understanding of infection/leprosy and are instructive for vaccine development.
PY - 2018 EP - 2920 T2 - Frontiers in immunology TI - Recombinant antigen induces high expression of multifunction T lymphocytes and is promising as a specific vaccine for leprosy. UR - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6315144/pdf/fimmu-09-02920.pdf VL - 9 SN - 1664-3224 ER -