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

作者：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^*

来源：European Journal of Immunology, 2011, 41(10): 2925-2936.

DOI：10.1002/eji.201141602

• DosR latency antigens and peptides
• Double- and monofunctional CD4(+) and CD8(+) T-cell responses
• Latent Mtb infection
• Mycobacterium tuberculosis

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-gamma, TNF-alpha 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-gamma(+) TNF-alpha(+) 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.

• 出版日期2011-10