Double- and monofunctional CD4 + and CD8 + T-cell responses to Mycobacterium tuberculosis DosR antigens and peptides in long-term latently infected individuals

Susanna Commandeur, May Y. Lin, Krista E. van Meijgaarden, Annemieke H. Friggen, Kees L.M.C. Franken, Jan W. Drijfhout, Gro E. Korsvold, Fredrik Oftung, Annemieke Geluk, Tom H.M. Ottenhoff*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review


More than 2 billion individuals are latently infected with Mycobacterium tuberculosis (Mtb). Knowledge of the key Mtb antigens and responding T-cell subsets mediating protection against Mtb is critical for developing improved tuberculosis (TB) vaccines. We previously reported that Mtb DosR-regulon-encoded antigens are recognized well by human T cells in association with control of Mtb infection. The characteristics of the responding T-cell subsets, however, remained unidentified. We have therefore studied the cytokine production and memory phenotypes of Mtb DosR-regulon-encoded antigen-specific T cells from individuals who had been infected with Mtb decades ago, yet never developed TB (long-term latent Mtb-infected individuals). Using multi-parameter flow cytometry and intracellular cytokine staining for IFN-γ, TNF-α and IL-2, we found double and single cytokine-producing CD4 + as well as CD8 + T cells to be the most prominent subsets, particularly IFN-γ + TNF-α + CD8 + T cells. The majority of these T cells comprised effector memory and effector T cells. Furthermore, CFSE labeling revealed strong CD4 + and CD8 + T-cell proliferative responses induced by several "immunodominant" Mtb DosR antigens and their specific peptide epitopes. These findings demonstrate the prominent presence of double- and monofunctional CD4 + and CD8 + T-cell responses in naturally protected individuals and support the possibility of designing Mtb DosR antigen-based TB vaccines.

Original languageEnglish
Pages (from-to)2925-2936
Number of pages12
JournalEuropean Journal of Immunology
Issue number10
Publication statusPublished - 1 Oct 2011

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