Dominance of CD86, transforming growth factor- beta 1, and interleukin-10 in Mycobacterium tuberculosis secretory antigen-activated dendritic cells regulates T helper 1 responses to mycobacterial antigens.
We report that stimulation of Mycobacterium tuberculosis (M. tuberculosis) secretory antigen (MTSA)-differentiated dendritic cells (DCs) and MTSA-matured DCs with M. tuberculosis cell extract (CE) down-regulated proinflammatory responses to CE-primed T (CE-T) cells by increasing surface expression of CD86 after CE stimulation. CE stimulation also decreased interleukin (IL)-12p40 and interferon (IFN)- gamma levels and increased IL-10 and transforming growth factor- beta 1 (TGF- beta 1) levels from these DCs. Blocking either CD86, IL-10, or TGF- beta with monoclonal antibodies before CE stimulation restored the attenuated T helper 1 (Th1) responses of CE-T cells. Conversely, treatment of these DCs with IL-12p70 and/or IFN- gamma completely restored Th1 responses from CE-T cells. These results indicate that M. tuberculosis secretory antigens down-regulate proinflammatory Th1 responses to mycobacteria by differentially modulating the cytokine profiles and surface densities of costimulatory molecules on DCs. Of importance, this down-regulation is independent of the maturation status of MTSA-activated DCs and can be rescued after treatment of DCs with IFN- gamma or IL-12.
Balkhi
Mumtaz Yaseen
MY
Immunology Group, International Center for Genetic Engineering and Biotechnology, Aruna Asaf Ali Marg, New Delhi, India.
Sinha
Aprajita
A
Natarajan
Krishnamurthy
K
D000818:Animals; D000942:Antigens, Bacterial / Q000276:immunology; D015703:Antigens, CD / Q000378:metabolism*; D051940:B7-2 Antigen; D002454:Cell Differentiation; D016207:Cytokines / Q000378:metabolism; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism; D015536:Down-Regulation; D005260:Female; D016753:Interleukin-10 / Q000378:metabolism*; D008562:Membrane Glycoproteins / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D009169:Mycobacterium tuberculosis / Q000276:immunology*; D018417:Th1 Cells / Q000276:immunology*; D016212:Transforming Growth Factor beta / Q000378:metabolism*; D053773:Transforming Growth Factor beta1
D000942:Antigens, Bacterial; D015703:Antigens, CD; D051940:B7-2 Antigen; C497965:Cd86 protein, mouse; D016207:Cytokines; D008562:Membrane Glycoproteins; C508961:Tgfb1 protein, mouse; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D016753:Interleukin-10