Disease-specific changes in gammadelta T cell repertoire and function in patients with pulmonary tuberculosis

Abstract

Although gammadelta T cells are known to contain the highest frequency of mycobacteria-reactive cells in humans and numerous studies have suggested that they play an important role in the initial immune response to Mycobacterium tuberculosis (Mtb), very few studies have attempted to analyze these cells in patients with active pulmonary tuberculosis. The aim of the present study was therefore to evaluate the consequences of infection on the number and activity of mycobacteria-reactive gammadelta T cells. Three-color flow cytometric analysis of blood and bronchoalveolar lavage gammadelta T cells of patients diagnosed with active pulmonary tuberculosis showed that compared with normal healthy subjects and patients with the unrelated pulmonary granulomatous diseases sarcoidosis and berylliosis the size of the mycobacteria-reactive Vgamma9+/Vdelta2+ gammadelta T cell subset in both the blood and lung was dramatically reduced. In addition, the Vgamma9+/Vdelta2+ cells left intact in patients with tuberculosis were refractory to in vitro stimulation by Mtb Ags, which are potent stimuli for these cells in normal subjects. Our results demonstrate for the first time a strong correlation between the absence or loss of the major Vgamma9+/Vdelta2+ Mtb-reactive subset of gammadelta T cells and manifestations of disease, consistent with the hypothesis that these gammadelta T cells play a role in the protective immune response to Mtb infection.