Cytokine mRNA Expression in Mononuclear Cells from Lymph Nodes of Tuberculous Lymphadenitis Patients after In Vitro Stimulation with the TSP Antigen of Mycobacterium tuberculosis H37Rv

ABSTRACT

We isolated Triton X-100 solubilized protein (TSP) antigen which may be preferentially associated with the cell wall of M. tuberculosis. In this study, the proliferative activities and cytokine mRNA expression patterns of the TSP antigen were investigated in peripheral blood mononuclear cells (PBMCs) and lymph node mononuclear cells (LNMCs) from 4 patients with tuberculous lymphadenitis. The results of the TSP antigen were compared with those of the PPD antigen, known as a major seretory protein antigen of M. tuberculosis. The peak proliferative response to the TSP by PBMCs was observed at 0.1 ug/ml, whereas that of LNMCs was at 1.0 ug/ml. All of the patients showed greater blastogenic responses for the PPD than those for the TSP. IFN-r, IL-2, and IL-2Ru mRNA production from PBMCs after stimulation with the TSP were greatly augmented after 48 hrs, whereas IL-4 and IL-10 mRNA were gradually suppressed. In addition, high levels of IL-12 p40 mRNA were detected by PBMCs to the TSP antigen at 3 hrs. Elevated IFN-r and IL-2 mRNA production were observed in freshly isolated LNMCs, whereas IL-4 mRNA production was undetectable in either freshly isolated or mycobacterial antigen-stimulated LNMCs. Furthermore, IL-10 mRNA expression from LNMCs was markedly increased by the PPD antigen, but it was considerably reduced by the TSP antigen after 18 hrs. These data suggest that the TSP antigen may be a strong inducer of cytokine mRNA such as IFN-r, IL-2, and IL-12 which are involved in Thl cell and macrophage activation, and inhibit IL-10 mRNA production in LNMCs. In conclusion, the TSP antigen can be used as a preferential Thl cell immunogen in tuberculous lymphadenitis.