Detailed characterization of human Mycobacterium tuberculosis specific HLA‐E restricted CD8+ T cells

• Published in: European journal of immunology Vol. 48; no. 2; pp. 293 - 305
• Main Authors: Prezzemolo, Teresa, Meijgaarden, Krista E., Franken, Kees L.M.C., Caccamo, Nadia, Dieli, Francesco, Ottenhoff, Tom H.M., Joosten, Simone A.
• Format: Journal Article
• Language: English
• Published: Germany Wiley Subscription Services, Inc 01.02.2018
• Subjects: Active TB; Antigens; Antigens, Bacterial - metabolism; CD8 antigen; CD8+ T cells; CD8-Positive T-Lymphocytes - immunology; Cell Proliferation; Cells, Cultured; Conserved Sequence - genetics; Cytokines; Cytokines - metabolism; Cytotoxicity; Cytotoxicity, Immunologic; Effector cells; Flow Cytometry; Histocompatibility antigen HLA; Histocompatibility Antigens Class I - genetics; Histocompatibility Antigens Class I - metabolism; HLA-A2 Antigen - metabolism; HLA-E Antigens; Humans; Immunophenotyping; Interferon; Interleukin 10; Interleukin 13; Interleukin 4; Lymphocyte Activation; Lymphocytes; Lymphocytes T; Mycobacterium tuberculosis; Mycobacterium tuberculosis - immunology; Peptides - metabolism; Perforin; Phenotypes; Tetramers; Th2; Th2 Cells - immunology; Transcription factors; Tuberculosis; Tuberculosis - immunology; Tuberculosis Vaccines - immunology; Vaccination; CD8+ T cells; Active TB; Tetramers; Cytokines; Th2
• ISSN: 0014-2980; 1521-4141; 1521-4141
• DOI: 10.1002/eji.201747184

HLA‐E presented antigens are interesting targets for vaccination given HLA‐Es’ essentially monomorphic nature. We have shown previously that Mycobacterium tuberculosis (Mtb) peptides are presented by HLA‐E to CD8+ effector T 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+ T cells in the circulation of patients with active tuberculosis (TB). HLA‐E restricted CD8+ T cells from TB patients produced more IL‐13 than cells from controls or subjects with latent tuberculosis infection (LTBI). Compared to total CD8+ T cells, HLA‐E restricted cells produced more IFNγ, IL‐4, IL‐10, and granulysin but less granzyme‐A. Moreover, compared to “classical” Mtb specific HLA‐A2 restricted CD8+ T cells, HLA‐E restricted CD8+ T cells produced less TNFα and perforin, but more IL‐4. In conclusion, HLA‐E restricted‐ Mtb specific cells can produce Th2 cytokines directly. The combination of tetramer staining with intracellular cytokine staining allowed the detailed characterization of T cells recognizing Mtb in the context of HLA‐E. Here we demonstrate that HLA‐E restricted, Mtb‐specific CD8+ T cells produce Th2 cytokines IL‐4 and IL‐13 directly and have a cytokine profile different from HLA‐A2 restricted Mtb specific T cells.