Journal Article

Dominance of CD86, Transforming Growth Factor-β1, and Interleukin-10 in <i>Mycobacterium tuberculosis</i> Secretory Antigen-Activated Dendritic Cells Regulates T Helper 1 Responses to Mycobacterial Antigens

Mumtaz Yaseen Balkhi, Aprajita Sinha and Krishnamurthy Natarajan

in The Journal of Infectious Diseases

Published on behalf of Infectious Diseases Society of America

Volume 189, issue 9, pages 1598-1609
Published in print May 2004 | ISSN: 0022-1899
Published online May 2004 | e-ISSN: 1537-6613 | DOI: http://dx.doi.org/10.1086/383328
Dominance of CD86, Transforming Growth Factor-β1, and Interleukin-10 in Mycobacterium tuberculosis Secretory Antigen-Activated Dendritic Cells Regulates T Helper 1 Responses to Mycobacterial Antigens

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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)-γ levels and increased IL-10 and transforming growth factor-β1 (TGF-β1) levels from these DCs. Blocking either CD86, IL-10, or TGF-β 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-γ 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-γ or IL-12.

Journal Article.  6869 words.  Illustrated.

Subjects: Infectious Diseases ; Immunology ; Public Health and Epidemiology ; Microbiology

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