Detailed characterization of human Mycobacterium tuberculosis specific HLA-E restricted CD8+TÂ cells
- Authors: Prezzemolo, Teresa; van Meijgaarden, Krista E.; Franken, Kees L.M.C.; Caccamo, Nadia; Dieli, Francesco; Ottenhoff, Tom H.M.; Joosten, Simone A
- Publication year: 2018
- Type: Articolo in rivista (Articolo in rivista)
- Key words: Active TB; CD8+TÂ cells; Cytokines; Tetramers; Th2; Immunology and Allergy; Immunology
- OA Link: http://hdl.handle.net/10447/273877
HLA-E presented antigens are interesting targets for vaccination given HLA-Esâ essentially monomorphic nature. We have shown previously that Mycobacterium tuberculosis (Mtb) peptides are presented by HLA-E to CD8+effector TÂ cells, but the precise phenotype and functional capacity of these cells remains poorly characterized. We have developed and utilized in this study a new protocol combining HLA-E tetramer with intracellular staining for cytokines, transcription factors and cytotoxic molecules to characterize these cells in depth. We confirm in this study the significantly increased ex vivo frequency of Mtb-peptide/HLA-E-TM+CD8+TÂ cells in the circulation of patients with active tuberculosis (TB). HLA-E restricted CD8+TÂ cells from TB patients produced more IL-13 than cells from controls or subjects with latent tuberculosis infection (LTBI). Compared to total CD8+TÂ cells, HLA-E restricted cells produced more IFNÎ³, IL-4, IL-10, and granulysin but less granzyme-A. Moreover, compared to âclassicalâ Mtb specific HLA-A2 restricted CD8+TÂ cells, HLA-E restricted CD8+TÂ cells produced less TNFÎ± and perforin, but more IL-4. In conclusion, HLA-E restricted- Mtb specific cells can produce Th2 cytokines directly.