PMID- 15116295 OWN - NLM STAT- MEDLINE DCOM- 20040604 LR - 20171116 IS - 0022-1899 (Print) IS - 0022-1899 (Linking) VI - 189 IP - 9 DP - 2004 May 1 TI - 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. PG - 1598-609 AB - 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. FAU - Balkhi, Mumtaz Yaseen AU - Balkhi MY AD - Immunology Group, International Center for Genetic Engineering and Biotechnology, Aruna Asaf Ali Marg, New Delhi, India. FAU - Sinha, Aprajita AU - Sinha A FAU - Natarajan, Krishnamurthy AU - Natarajan K LA - eng GR - AI-75320/AI/NIAID NIH HHS/United States PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Research Support, U.S. Gov't, P.H.S. DEP - 20040416 PL - United States TA - J Infect Dis JT - The Journal of infectious diseases JID - 0413675 RN - 0 (Antigens, Bacterial) RN - 0 (Antigens, CD) RN - 0 (B7-2 Antigen) RN - 0 (Cd86 protein, mouse) RN - 0 (Cytokines) RN - 0 (Membrane Glycoproteins) RN - 0 (Tgfb1 protein, mouse) RN - 0 (Transforming Growth Factor beta) RN - 0 (Transforming Growth Factor beta1) RN - 130068-27-8 (Interleukin-10) SB - IM MH - Animals MH - Antigens, Bacterial/immunology MH - Antigens, CD/*metabolism MH - B7-2 Antigen MH - Cell Differentiation MH - Cytokines/metabolism MH - Dendritic Cells/*immunology/metabolism MH - *Down-Regulation MH - Female MH - Interleukin-10/*metabolism MH - Membrane Glycoproteins/*metabolism MH - Mice MH - Mice, Inbred BALB C MH - Mycobacterium tuberculosis/*immunology MH - Th1 Cells/*immunology MH - Transforming Growth Factor beta/*metabolism MH - Transforming Growth Factor beta1 EDAT- 2004/04/30 05:00 MHDA- 2004/06/05 05:00 CRDT- 2004/04/30 05:00 PHST- 2003/09/23 00:00 [received] PHST- 2003/11/08 00:00 [accepted] PHST- 2004/04/30 05:00 [pubmed] PHST- 2004/06/05 05:00 [medline] PHST- 2004/04/30 05:00 [entrez] AID - JID31827 [pii] AID - 10.1086/383328 [doi] PST - ppublish SO - J Infect Dis. 2004 May 1;189(9):1598-609. doi: 10.1086/383328. Epub 2004 Apr 16.