title: Human pleural B-cells regulate IFN-γ production by local T-cells and NK cells in a Mycobacterium tuberculosis-induced delayed hypersensitivity reaction.
abstract: DTH (delayed type hypersensitivity) reactions are secondary cellular immune responses that appear 24-72 h after antigen exposure. Tuberculous pleurisy is a common manifestation of extrapulmonary TB (tuberculosis) and is considered a human model of Th1-mediated DTH. In order to identify functional cross-talk among cellular populations sited in this inflammatory microenvironment, we analysed phenotypic and functional features of human B-cells isolated from the PF (pleural fluid) of TB patients. Freshly isolated PF-B-cells displayed a lower expression of CD20, CD1d and HLA-DR, and a higher expression of CD95, CD38, CD25, CXCR3 (CXC chemokine receptor 3) and CXCR4 (CXC chemokine receptor 4) than their PB (peripheral blood) counterparts, suggesting a non-classical in situ activation. Although memory PF-T-cell frequencies were increased, the frequencies of memory PF-B-cells were not. We demonstrated that, upon stimulation with γ-irradiated M. tuberculosis, mycobacterially secreted proteins or a lectin mitogen, PF-B-cells had a strong activation and produced IL-10 by a mechanism that was dependent on bystander activation of CD19(-) PF cells. Besides, within PF cells, B-cells diminished in vitro M. tuberculosis-induced IFN (interferon)-γ production by T-cells and NK (natural killer) cells in an IL-10-dependent manner. Finally, we found that the lower the frequency of B-cells, the higher the ratio of IFN-γ/IL-10 within PF. Thus our results suggest that B-cells can regulate a human DTH reaction induced by M. tuberculosis.
authors.affiliation: *Inmunologia de Enfermedades Respiratorias, Instituto de Medicina Experimental (IMEX)-CONICET, Academia Nacional de Medicina, Pacheco de Melo 3081, 1425, Buenos Aires, Argentina.
authors.forename: Pablo
authors.initials: P
authors.lastname: Schierloh
authors.affiliation: *Inmunologia de Enfermedades Respiratorias, Instituto de Medicina Experimental (IMEX)-CONICET, Academia Nacional de Medicina, Pacheco de Melo 3081, 1425, Buenos Aires, Argentina.
authors.forename: Verónica
authors.initials: V
authors.lastname: Landoni
authors.affiliation: *Inmunologia de Enfermedades Respiratorias, Instituto de Medicina Experimental (IMEX)-CONICET, Academia Nacional de Medicina, Pacheco de Melo 3081, 1425, Buenos Aires, Argentina.
authors.forename: Luciana
authors.initials: L
authors.lastname: Balboa
authors.affiliation: †División de Neumonología, Hospital F.J Muñiz, Uspallata 2272, 1282, Buenos Aires, Argentina.
authors.forename: Rosa M
authors.initials: RM
authors.lastname: Musella
authors.affiliation: †División de Neumonología, Hospital F.J Muñiz, Uspallata 2272, 1282, Buenos Aires, Argentina.
authors.forename: Jorge
authors.initials: J
authors.lastname: Castagnino
authors.affiliation: ‡Instituto de Tisioneumonologia Dr R. F Vaccarezza, Universidad de Buenos Aires, Av. Velez Sarfield 405, 1281, Buenos Aires, Argentina.
authors.forename: Eduardo
authors.initials: E
authors.lastname: Moraña
authors.forename: Graciela C
authors.initials: GC
authors.lastname: de Casado
authors.affiliation: †División de Neumonología, Hospital F.J Muñiz, Uspallata 2272, 1282, Buenos Aires, Argentina.
authors.forename: Domingo
authors.initials: D
authors.lastname: Palmero
authors.affiliation: *Inmunologia de Enfermedades Respiratorias, Instituto de Medicina Experimental (IMEX)-CONICET, Academia Nacional de Medicina, Pacheco de Melo 3081, 1425, Buenos Aires, Argentina.
authors.forename: María C
authors.initials: MC
authors.lastname: Sasiain
mesh_terms: D001402:B-Lymphocytes / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D006968:Hypersensitivity, Delayed / Q000276:immunology*; D007111:Immunity, Cellular / Q000276:immunology; D007371:Interferon-gamma / Q000096:biosynthesis*; D016753:Interleukin-10 / Q000276:immunology; D007694:Killer Cells, Natural / Q000276:immunology / Q000378:metabolism*; D009169:Mycobacterium tuberculosis / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism*; D014396:Tuberculosis, Pleural / Q000276:immunology / Q000382:microbiology*
chemical_list: C508609:IL10 protein, human; D016753:Interleukin-10; D007371:Interferon-gamma