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Mycobacterium bovis bacillus Calmette–Guérin‐infected dendritic cells potently activate autologous T cells via a B7 and interleukin‐12‐dependent mechanism
Author(s) -
Cheadle Eleanor J.,
Selby Peter J.,
Jackson Andrew M.
Publication year - 2003
Publication title -
immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.297
H-Index - 133
eISSN - 1365-2567
pISSN - 0019-2805
DOI - 10.1046/j.1365-2567.2003.01543.x
Subject(s) - biology , secretion , mycobacterium bovis , microbiology and biotechnology , interleukin 12 , interferon gamma , priming (agriculture) , il 2 receptor , cytokine , cd8 , cytotoxic t cell , immunology , immune system , mycobacterium tuberculosis , t cell , medicine , in vitro , tuberculosis , pathology , biochemistry , botany , germination
Summary Mycobacteria are potent adjuvants, can survive intracellularly and have been safely used for many years as vaccines against tuberculosis and leprosy. They are thus important potential vectors for recombinant vaccines. Many of their adjuvant properties are mediated following phagocytosis by dendritic cells (DC), which are in turn critical for priming naïve T cells. Although the maturation of DC in response to mycobacteria, such as Mycobacterium bovis bacillus Calmette–Guérin (BCG), is well described the subsequent responses of autologous T cells to mycobacterium‐infected DC remains uncharacterized. In our experiments DC infected with BCG expressed more co‐stimulatory molecules than tumour‐necrosis factor‐α (TNF‐α) ‐treated DC and stimulated more potent mixed leucocyte reactions. When autologous T cells were co‐cultured with BCG‐exposed DC they became highly activated, as determined by display of CD25, CD54 and CD71 on both CD4 + and CD8 + cells. In contrast, the response of T cells to TNF‐α‐matured DC was significantly less. Cytokine production from T cells cultured with BCG‐exposed DC was enhanced with elevated secretion of interleukin‐2 (IL‐2), IL‐10 and interferon‐γ (IFN‐γ) and was produced by both CD4 + and CD8 + lymphocytes as determined by intracellular staining. In particular, IFN‐γ secretion was increased from 50 pg/ml to 25 000 pg/ml and IL‐10 secretion increased from 20 pg/ml to 300 pg/ml in BCG‐exposed DC co‐cultures. Blocking antibodies to B7.1 and B7.2 or IL‐12 significantly reduced the secretion of IFN‐γ and reductions were also seen in the expression of CD25 and CD71 by CD4 + cells. These data demonstrate that mycobacterially infected DC are particularly potent activators of autologous T cells compared to TNF‐α‐exposed DC and that the resultant T cells are functionally superior.