Increased Susceptibility to Apoptosis of CD56 super(dim)CD16 super(+) NK Cells Induces the Enrichment of IFN- gamma -Producing CD56 super(bright) Cells in Tuberculous Pleurisy

Tuberculous pleuritis is a good model for the study of specific cells at the site of active Mycobacterium tuberculosis (Mtb) infection. We investigated the frequency and phenotype of NK cells in paired samples of peripheral blood and pleural fluid (PF) from patients with tuberculosis (TB) or parapneumonic infection. We demonstrated for the first time a reduction of NK cells in PF from TB with an enrichment in the CD56 super(bright)CD16 super(-) subset. In agreement, in PF NK cells we observed an increased expression of CD94, NKG2A, CD62L, and CCR7 molecules and lower expression of Bcl-2 and perforin. The activation markers CD69 and HLA-DR were also increased. The enrichment in the CD56 super(bright) subset was due to an increased susceptibility to apoptosis of CD56 super(+)CD16 super(+) NK cells mediated by heat-labile and stable soluble factors present in tuberculous effusions and not in PF from other etiologies. Furthermore, in TB patients, Mtb-induced IFN- gamma production by PF NK cells was not dependent on the presence of CD3 super(+), CD19 super(+), and CD14 super(+) cells, suggesting a direct interaction of CD56 super(bright) cells with Mtb and/or the involvement of other accessory cells present at the site of Mtb infection.