RESUMEN
Tuberculous pleural effusion is characterized by a T helper type 1 (Th1) profile, but an excessive Th1 response may also cause tissue damage that might be controlled by regulatory mechanisms. In the current study we investigated the role of regulatory T cells (Treg ) in the modulation of Th1 responses in patients with tuberculous (TB) pleurisy. Using flow cytometry we evaluated the proportion of Treg (CD4(+) CD25(high) forkhead box protein 3(+) ), interferon (IFN)-γ and interleukin (IL)-10 expression and CD107 degranulation in peripheral blood (PB) and pleural fluid (PF) from patients with TB pleurisy. We demonstrated that the proportion of CD4(+) CD25(+) , CD4(+) CD25(high) FoxP3(+) and CD8(+) CD25(+) cells were increased in PF compared to PB samples. Mycobacterium tuberculosis stimulation increased the proportion of CD4(+) CD25(low/neg) IL-10(+) in PB and CD4(+) CD25(low/neg) IFN-γ(+) in PF; meanwhile, CD25(high) mainly expressed IL-10 in both compartments. A high proportion of CD4(+) CD107(+) and CD8(+) CD107(+) cells was observed in PF. Treg depletion enhanced the in-vitro M. tuberculosis-induced IFN-γ and CD4(+) and CD8(+) degranulation responses and decreased CD4(+) IL-10(+) cells in PF. Our results demonstrated that in TB pleurisy Treg cells effectively inhibit not only IFN-γ expression but also the ability of CD4(+) and CD8(+) cells to degranulate in response to M. tuberculosis.
Asunto(s)
Degranulación de la Célula/inmunología , Interferón gamma/inmunología , Proteína 1 de la Membrana Asociada a los Lisosomas/inmunología , Derrame Pleural/inmunología , Linfocitos T Reguladores/inmunología , Tuberculosis Pleural/inmunología , Adulto , Linfocitos T CD8-positivos/inmunología , Femenino , Factores de Transcripción Forkhead/metabolismo , Humanos , Interleucina-10/metabolismo , Subunidad alfa del Receptor de Interleucina-2/metabolismo , Leucocitos Mononucleares/metabolismo , Masculino , Mycobacterium tuberculosis/inmunología , Adulto JovenRESUMEN
Tuberculous pleurisy is a naturally occurring site of Mycobacterium tuberculosis (Mtb) infection. Herein, we describe the expression of activation, natural killer (NK) and cell migration markers, as well as effector functions from gammadeltaT cells in peripheral blood (PB) and pleural effusion (PE) from tuberculosis patients (TB). We observed a decreased percentage of circulating gammadeltaT from TB patients and differential expression of NK as well as of chemokine receptors on PB and PE. Two subsets of gammadeltaT cells were differentiated by the CD3/gammadeltaT cell receptor (gammadeltaTCR) complex. The gammadeltaTCR(low) subset had a higher CD3 to TCR ratio and was enriched in Vdelta2(+) cells, whereas most Vdelta1(+) cells belonged to the gammadeltaTCR(high) subset. In PB from TB, most gammadeltaTCR(high) were CD45RA(+)CCR7(-) and gammadeltaTCR(low) were CD45RA(+/-)CCR7(+)CXCR3(+). In the pleural space the proportion of CD45RA(-)CCR7(+)CXCR3(+) cells was higher. Neither spontaneous nor Mtb-induced interferon (IFN)-gamma production was observed in PB-gammadeltaT cells from TB; however, PE-gammadeltaT cells showed a strong response. Both PB- and PE-gammadelta T cells expressed surface CD107a upon stimulation with Mtb. Notably, PE-gammadeltaTCR(low) cells were the most potent effector cells. Thus, gammadeltaT cells from PB would acquire a further activated phenotype within the site of Mtb infection and exert full effector functions. As gammadeltaT cells produce IFN-gamma within the pleural space, they would be expected to play a beneficial role in tuberculous pleurisy by helping to maintain a T helper type 1 profile.