CD4-CD8-αβ and γδ T cells display inflammatory and regulatory potentials during human tuberculosis

• Published in: PloS one Vol. 7; no. 12; p. e50923
• Main Authors: Pinheiro, Melina B, Antonelli, Lis R, Sathler-Avelar, Renato, Vitelli-Avelar, Danielle M, Spindola-de-Miranda, Silvana, Guimarães, Tânia M P D, Teixeira-Carvalho, Andrea, Martins-Filho, Olindo A, Toledo, Vicente P C P
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 11.12.2012; Public Library of Science (PLoS)
• Subjects: Activation; Adolescent; Adult; Aged; Antigens; Bacteriology; Biology; CD4 antigen; CD4-Positive T-Lymphocytes - cytology; CD4-Positive T-Lymphocytes - immunology; CD69 antigen; CD8 antigen; CD8-Positive T-Lymphocytes - cytology; CD8-Positive T-Lymphocytes - immunology; Cell Lineage - immunology; Clinical aspects; Cloning; Cytokines; Female; Females; Histocompatibility antigen HLA; HLA-DR Antigens - metabolism; Humans; Immunity; Immunology; Immunoregulation; Infections; Infectious diseases; Inflammation; Interferon; Interleukin 10; Interleukin-10 - metabolism; Lymphocyte Activation - immunology; Lymphocytes; Lymphocytes T; Male; Medicine; Middle Aged; Mycobacterium tuberculosis; Mycobacterium tuberculosis - immunology; Mycobacterium tuberculosis - pathogenicity; Patients; Peripheral blood; Receptors; Receptors, Antigen, T-Cell, alpha-beta - immunology; Receptors, Antigen, T-Cell, alpha-beta - metabolism; Receptors, Antigen, T-Cell, gamma-delta - immunology; Receptors, Antigen, T-Cell, gamma-delta - metabolism; Rheumatoid arthritis; T cell receptors; T-cell receptor; T-Lymphocyte Subsets - cytology; T-Lymphocyte Subsets - immunology; Tuberculosis; Tuberculosis - immunology; Tuberculosis - microbiology; Tumor necrosis factor-TNF; γ-Interferon
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0050923

T-cells play an important role controlling immunity against pathogens and therefore influence the outcome of human diseases. Although most T-lymphocytes co-express either CD4 or CD8, a smaller T-cell subset found the in the human peripheral blood that expresses the αβ or γδ T-cell-receptor (TCR) lacks the CD4 and CD8 co-receptors. These double negative (DN) T-cells have been shown to display important immunological functions in human diseases. To better understand the role of DN T-cells in human Mycobacterium tuberculosis, we have characterized their frequency, activation and cytokine profile in a well-defined group of tuberculosis patients, categorized as severe and non-severe based on their clinical status. Our data showed that whereas high frequency of αβ DN T-cells observed in M. tuberculosis-infected patients are associated with disease severity, decreased proportion of γδ DN T-cells are found in patients with severe tuberculosis. Together with activation of CD4(+) and CD8(+) T-cells, higher frequencies of both αβ and γδ DN T-cells from tuberculosis patients also express the chronic activation marker HLA-DR. However, the expression of CD69, an early activation marker, is selectively observed in DN T-cells. Interestingly, while αβ and γδ DN T-cells from patients with non-severe tuberculosis display a pro-inflammatory cytokine profile, characterized by enhanced IFN-γ, the γδ DN T-cells from patients with severe disease express a modulatory profile exemplified by enhanced interleukin-10 production. Overall, our findings suggest that αβ and γδ DN T-cell present disparate immunoregulatory potentials and seems to contribute to the development/maintenance of distinct clinical aspects of TB, as part of the complex immunological network triggered by the TB infection.