Tuberculous pleurisy derived NK cells expressing high ICAM-1 levels exert costimulatory effect in T cells: In vivo unconventional local accessory cell function of NK.

SCHIERLOH P; YOKOBORI N; MUSELLA R; CASTAGNINO J; DE LA BARRERA SS; SASIAIN MC

Berlin, Alemania

Congreso; 2nd European Congress of Immunology. “Immunity for Life, Immunology for Health”.; 2009

European Federation of Immunological Societies (EFIS)

Tuberculous pleurisy, one of the most common manifestations of extrapulmonary tuberculosis, is characterized by a T cell mediated hypersensitivity reaction along with Th1 immune profile. In this study, we have investigated functional cross-talk among human T and NK cells in tuberculous pleurisy. We found that, endogenously activated, pleural fluid derived NK cells (PFNK) expressed higher ICAM-1 levels than its peripheral blood counterparts (MFI PFNK=148±9; PB-NK=55±10, p< 0.0005, N=12). Furthermore, practically all PF-NK that express IFN-ã upon Mycobacterium tuberculosis (Mtb) stimulation have ICAM-1high phenotype (% IFN-ã+/ICAM-1high= 92±7%; IFN-ã+/ICAM-1dim=7±3%, p< 0.05, N=5). In order to explore functional consequences for enhanced ICAM-1 in PF-NK, we conducted co-cultures with autologous PF-T cells, and found that the presence of PF-NK increased % CD69+ T and that neutralizing mAb anti-ICAM-1 inhibit this effect to basal levels (Fold increase % CD69+ T cell with: PF-NK+IgG1=2.9±0.1; PF-NK+anti-ICAM-1=1.1±0.2, p< 0.05, N=5). Besides, upon in vitro stimulation with monokines, normal blood derived resting NK cells increased ICAM-1 expression (p< 0.001, N=5) leading to conjugate formation (N=3), co-stimulation (N=4) and Th1 polarization (N=3) of autologous T cells. These results provide evidence of accessory cell function of human NK in a physiologically relevant inflammatory site, suggesting that NK contribute to adaptative immune response by a direct cell-contact-dependent mechanism in the context of Mtb infection.