Cellular immune responses are responsible for protection as well as pathology in tuberculosis, and are mediated/regulated by a complex network of pro-inflammatory, T helper type 1 (Th1) and T helper type 2 (Th2) cytokines.
In this work, we have studied the secretion of pro-inflammatory cytokines tumor necrosis factor-alpha (TNF-α), interleukin (IL)-6, IL-8 and IL-1 beta (IL-1β); Th1 cytokines interferon-gamma (IFN-γ), IL-2 and tumor necrosis factor-beta (TNF-β); and Th2 cytokines IL-4, IL-5 and IL-10 by peripheral blood mononuclear cells (PBMCs) of pulmonary tuberculosis patients. PBMCs were cultured in vitro in the absence and presence of complex mycobacterial antigens and peptides corresponding to 11 regions of difference (RD) of Mycobacterium tuberculosis, which are deleted/absent in all vaccine strains of Mycobacterium bovis bacillus Calmette Guerin (BCG). The culture supernatants were tested for secreted cytokines by FlowCytomix assay. PBMCs from majority of patients (53-100%) spontaneously secreted detectable concentrations of all cytokines tested, except for IL2 (29%) and IL-10 (41%). The profiles of proinflmmatory cytokines were largely similar for various complex antigens or RD peptides. However, with respect to Th1 and Th2 cytokines, the antigens could be divided into three groups; first group with Th1-bias (culture filtrate of M. tuberculosis, RD1, RD5, RD7, RD9 and RD10), the second group with Th2-bias (whole cells and cell walls of M. tuberculosis, RD12, RD13 and RD15), and the third group without Th1/Th2-bias (M. bovis BCG, RD4, RD6 and RD11).
The complex mycobacterial antigens and RD proteins with Th1- and Th2-biases may have roles in protection and pathogenesis of tuberculosis, respectively.
Authors: Mustafa AS, Al-Saidi F, Mahmoud El-Shamy AS, Al-Attiyah R
Read Full Article