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Double‐ and monofunctional CD4 + and CD8 + T‐cell responses to Mycobacterium tuberculosis DosR antigens and peptides in long‐term latently infected individuals
Author(s) -
Commandeur Susanna,
Lin May Y.,
van Meijgaarden Krista E.,
Friggen Annemieke H.,
Franken Kees L. M. C.,
Drijfhout Jan W.,
Korsvold Gro E.,
Oftung Fredrik,
Geluk Annemieke,
Ottenhoff Tom H. M.
Publication year - 2011
Publication title -
european journal of immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.272
H-Index - 201
eISSN - 1521-4141
pISSN - 0014-2980
DOI - 10.1002/eji.201141602
Subject(s) - biology , antigen , mycobacterium tuberculosis , cytotoxic t cell , cd8 , t cell , effector , epitope , virology , immunology , cytokine , tuberculosis , immune system , in vitro , genetics , medicine , pathology
Abstract 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.