THE PD-1/B7-H1-MEDIATED PRO-APOPTOTIC ACTIVITY OF DENDRITIC CELLS AS A POSSIBLE MECHANISM OF ANTIGEN-SPECIFIC RESPONSE FAILURE IN PATIENTS WITH PULMONARY TUBERCULOSIS

Abstract

Abstract. The aim of present study was to investigate PD-1/B7-H1-mediated induction of T-cell apoptosis/ anergy, a suggested mechanism of reduced antigen-specific immune response against M. tuberculosis. We examined 76 patients with pulmonary tuberculosis (PT) who differed in levels of proliferative response to specific antigen (purified protein derivative, PPD). It was revealed that in vitro generated dendritic cells (DCs) from the patient’s blood monocytes with GMCSF+IFNα, were characterized by increased B7-H1 expression, upregulation of IL-10 production, and reduced allostimulatory activity in mixed lymphocyte culture (MLC). Moreover, DCs of PT patients were able to enhance T-cell apoptosis, and to block T-cell division in MLC. Thus, the patients’ DCs exhibited the higher tolerogenic potential since these DCs could induce apoptosis/anergy in responsive T-cells via PD-1/B7-H1-mediated pathway combined with IL-10 effects. It was shown that neutralizing anti-PD1-antibodies partially abolished the pro-apoptogenic/tolerogenic effect of DCs. The revealed phenomenon of PD-1/B7-H1-mediated pro-apoptogenic activity should be of obvious clinical significance, since the cytotoxic/tolerogenic potential of DCs was especially pronounced in the patients with low antigen-specific response to PPD.

Keywords

• b7-h1
• dendritic cells
• pd-1
• т-cells, apoptosis
• pulmonary tuberculosis