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.
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Research Article|
May 29 2014
Human pleural B-cells regulate IFN-γ production by local T-cells and NK cells in a Mycobacterium tuberculosis-induced delayed hypersensitivity reaction
Pablo Schierloh;
*Inmunologia de Enfermedades Respiratorias, Instituto de Medicina Experimental (IMEX)-CONICET, Academia Nacional de Medicina, Pacheco de Melo 3081, 1425, Buenos Aires, Argentina
Correspondence: Dr Pablo Schierloh (email lp_shier@hotmail.com).
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Verónica Landoni;
Verónica Landoni
*Inmunologia de Enfermedades Respiratorias, Instituto de Medicina Experimental (IMEX)-CONICET, Academia Nacional de Medicina, Pacheco de Melo 3081, 1425, Buenos Aires, Argentina
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Luciana Balboa;
Luciana Balboa
*Inmunologia de Enfermedades Respiratorias, Instituto de Medicina Experimental (IMEX)-CONICET, Academia Nacional de Medicina, Pacheco de Melo 3081, 1425, Buenos Aires, Argentina
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Rosa M. Musella;
Rosa M. Musella
†División de Neumonología, Hospital F.J Muñiz, Uspallata 2272, 1282, Buenos Aires, Argentina
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Jorge Castagnino;
Jorge Castagnino
†División de Neumonología, Hospital F.J Muñiz, Uspallata 2272, 1282, Buenos Aires, Argentina
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Eduardo Moraña;
Eduardo Moraña
‡Instituto de Tisioneumonologia Dr R. F Vaccarezza, Universidad de Buenos Aires, Av. Velez Sarfield 405, 1281, Buenos Aires, Argentina
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Graciela C. de Casado;
Graciela C. de Casado
†División de Neumonología, Hospital F.J Muñiz, Uspallata 2272, 1282, Buenos Aires, Argentina
‡Instituto de Tisioneumonologia Dr R. F Vaccarezza, Universidad de Buenos Aires, Av. Velez Sarfield 405, 1281, Buenos Aires, Argentina
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Domingo Palmero;
Domingo Palmero
†División de Neumonología, Hospital F.J Muñiz, Uspallata 2272, 1282, Buenos Aires, Argentina
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María C. Sasiain
María C. Sasiain
*Inmunologia de Enfermedades Respiratorias, Instituto de Medicina Experimental (IMEX)-CONICET, Academia Nacional de Medicina, Pacheco de Melo 3081, 1425, Buenos Aires, Argentina
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Publisher: Portland Press Ltd
Received:
November 25 2013
Revision Received:
February 10 2014
Accepted:
April 01 2014
Accepted Manuscript online:
April 01 2014
Online ISSN: 1470-8736
Print ISSN: 0143-5221
© The Authors Journal compilation © 2014 Biochemical Society
2014
Clin Sci (Lond) (2014) 127 (6): 391–403.
Article history
Received:
November 25 2013
Revision Received:
February 10 2014
Accepted:
April 01 2014
Accepted Manuscript online:
April 01 2014
Citation
Pablo Schierloh, Verónica Landoni, Luciana Balboa, Rosa M. Musella, Jorge Castagnino, Eduardo Moraña, Graciela C. de Casado, Domingo Palmero, María C. Sasiain; Human pleural B-cells regulate IFN-γ production by local T-cells and NK cells in a Mycobacterium tuberculosis-induced delayed hypersensitivity reaction. Clin Sci (Lond) 1 September 2014; 127 (6): 391–403. doi: https://doi.org/10.1042/CS20130769
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