Article ID Journal Published Year Pages File Type
2402009 Tuberculosis 2007 11 Pages PDF
Abstract

SummaryDendritic cells (DC) likely play important and unique roles in the generation of protective immunity to mycobacteria. In order to clarify their contributions, bone marrow-derived DC loaded with Mycobacterium tuberculosis sonicate antigens were used to stimulate T cell proliferation both in vitro and in vivo and to vaccinate C57BL/6 mice against subsequent challenge with virulent mycobacteria. Antigen-pulsed DC developed in fetal calf serum (FCS-DC), but not DC developed in normal mouse serum (NMS-DC), stimulated significant proliferation of both naïve and immune T cells in vitro. The difference between cell populations developed in FCS and NMS in the content of CD11c+ cells and in production of key cytokines indicated that NMS is less supportive for the development of activated DC. However, following adoptive transfer of a single dose of antigen-pulsed DC into naive recipients, NMS-DC induced T cells that proliferated in response to mycobacterial antigen, whereas FCS-DC stimulated strong non-specific proliferation. Vaccination with two doses of antigen-pulsed NMS-DC by the subcutaneous route induced significant protection against intravenous challenge with a moderate dose of virulent M. tuberculosis. DC-vaccinated mice exhibited significant reductions in bacillary loads in the lungs and spleens, and markedly reduced lung pathology. Three doses of antigen-pulsed NMS-DC induced a significant increase in survival time following high dose challenge, which correlated with a significant increase in IFN-γ-producing cells in both lung and lymphoid tissues, as assessed by the ELISPOT assay. Taken together, these results indicate that DC play a critical role in the induction of protective resistance against virulent mycobacterial challenge accompanied by the development of antigen-reactive, IFN-γ-producing T cells, and that their antigenic specificity is influenced by the culture conditions under which the DC are developed.

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