International Immunology Advance Access originally published online on September 26, 2005
International Immunology 2005 17(11):1439-1446; doi:10.1093/intimm/dxh322
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Superior T cell activation by ESAT-6 as compared with the ESAT-6–CFP-10 complex
1 Department of Infection, Immunity and Inflammation, Medical Sciences Building, University of Leicester, Leicester LE1 9HN, UK
2 Allergy Research Group, Institute of Infection, Immunity and Inflammation, University of Nottingham, Nottingham, UK
3 Department of Biochemistry, University of Leicester, Leicester LE1 9HN, UK
4 Department of Infectious Diseases, Leicester Royal Infirmary, Leicester, UK
Correspondence to: L. Ziegler-Heitbrock; E-mail: lzh1{at}le.ac.uk
Using intracellular cytokine staining we show herein that T cells will respond to short-term (6 h) activation with phorbol ester plus ionomycin by production of tumor necrosis factor (TNF), IFN-
or both. Here CD4 T cells preferentially produce TNF and CD8 cells IFN-. The same pattern is seen when T cells are activated with the Mycobacterium tuberculosis protein early secretory antigenic target-6 (ESAT-6). Responses with >0.02% IFN-+ CD3 cells were seen in 8 of 10 patients diagnosed with tuberculosis and in 12 of 14 healthy individuals selected for likely exposure to M. tuberculosis. T cell responses to the 1:1 complex of ESAT-6 and culture filtrate protein-10 (CFP-10) were inferior to ESAT-6 alone, and only reached the level of T cell response achieved with CFP-10 alone. Extending the time of incubation to 18 h leads to an increased response to the complex, but it still reached only the level of CFP-10 alone. In vitro digestion with lysosomal enzymes cathepsin L and S at 2000:1 protein to enzyme ratio demonstrates rapid digestion of the individual proteins while the ESAT-6–CFP-10 complex is resistant. The data suggest that the natural complex of ESAT-6–CFP-10 is less amenable to antigen processing leading to a lower T cell response as compared with the individual proteins.
Keywords: antigen presentation, T cells, tuberculosis
Transmitting editor: S. Kaufmann
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