title: Gamma delta T cell responses associated with the development of tuberculosis in health care workers.
abstract: This study evaluated T cell immune responses to purified protein derivative (PPD) and Mycobacterium tuberculosis (Mtb) in health care workers who remained free of active tuberculosis (HCWs w/o TB), health care workers who went on to develop active TB (HCWs w/TB), non-health care workers who were TB free (Non-HCWs) and tuberculosis patients presenting with minimal (Min TB) or advanced (Adv TB) disease. Peripheral blood mononuclear cells (PBMC) were stimulated with Mtb and PPD and the expression of T cell activation markers CD25+ and HLA-DR+, intracellular IL-4 and IFN-gamma production and cytotoxic responses were evaluated. PBMC from HCWs who developed TB showed decreased percentages of cells expressing CD8+CD25+ in comparison to HCWs who remained healthy. HCWs who developed TB showed increased gammadelta TCR+ cell cytotoxicity and decreased CD3+gammadelta TCR- cell cytotoxicity in comparison to HCWs who remained healthy. PBMC from TB patients with advanced disease showed decreased percentages of CD25+CD4+ and CD25+CD8+ T cells that were associated with increased IL-4 production in CD8+ and gammadelta TCR+ phenotypes, in comparison with TB patients presenting minimal disease. TB patients with advanced disease showed increased gammadelta TCR+ cytotoxicity and reduced CD3+gammadelta TCR- cell cytotoxicity. Our results suggest that HCWs who developed TB show an early compensatory mechanism involving an increase in lytic responses of gammadelta TCR+ cells which did not prevent TB.
authors.affiliation: Centro de Malária e Outras Doenças Tropicais, Instituto de Higiene e Medicina Tropical, Universidade Nova de Lisboa, Rua da Junqueira 96, 1394-008 Lisbon, Portugal. dordway@lamar.colostate.edu
authors.forename: Diane J
authors.initials: DJ
authors.lastname: Ordway
authors.forename: Luisa
authors.initials: L
authors.lastname: Pinto
authors.forename: Leonor
authors.initials: L
authors.lastname: Costa
authors.forename: Marta
authors.initials: M
authors.lastname: Martins
authors.forename: Clara
authors.initials: C
authors.lastname: Leandro
authors.forename: Miguel
authors.initials: M
authors.lastname: Viveiros
authors.forename: Leonard
authors.initials: L
authors.lastname: Amaral
authors.forename: Maria J
authors.initials: MJ
authors.lastname: Arroz
authors.forename: Fernando A
authors.initials: FA
authors.lastname: Ventura
authors.forename: Hazel M
authors.initials: HM
authors.lastname: Dockrell
mesh_terms: D000328:Adult; D003602:Cytotoxicity, Immunologic; D005260:Female; D006282:Health Personnel; D006801:Humans; D066298:In Vitro Techniques; D017758:Infectious Disease Transmission, Patient-to-Professional; D007371:Interferon-gamma / Q000097:blood; D015847:Interleukin-4 / Q000097:blood; D008213:Lymphocyte Activation; D018655:Lymphocyte Count; D008297:Male; D008875:Middle Aged; D009784:Occupational Diseases / Q000209:etiology / Q000276:immunology; D011174:Portugal; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000097:blood; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D014397:Tuberculosis, Pulmonary / Q000209:etiology* / Q000276:immunology* / Q000635:transmission
chemical_list: D016692:Receptors, Antigen, T-Cell, gamma-delta; D015847:Interleukin-4; D007371:Interferon-gamma