Down‐Regulation of T Helper 1 Responses to Mycobacterial Antigens Due to Maturation of Dendritic Cells by 10‐kDa<i>Mycobacterium tuberculosis</i>Secretory Antigen

Abstract

Interactions of 10-kDa Mycobacterium tuberculosis secretory antigen (MTSA) with dendritic cells (DCs) were investigated to elucidate the role of secretory antigens in regulating immune responses to M. tuberculosis early in the course of infection. MTSA induced the maturation of different DC subsets. The cytokine profiles of these DCs were characteristic to each DC subset. Of interest, coculture of M. tuberculosis whole-cell extract (CE)-pulsed, MTSA-matured DCs with CE-specific T cells led to a marked reduction in interleukin (IL)-2 and interferon (IFN)-gamma production, thereby down-regulating proinflammatory responses to mycobacterial antigens. Attenuation of IL-2 and IFN-gamma levels of CE-specific T cells also was obtained when M. tuberculosis culture filtrate protein-activated DCs were employed as antigen-presenting cells, which suggests that MTSAs induce maturation of DCs at sites of infection, probably to down-regulate proinflammatory immune responses to mycobacteria that may subsequently be released from infected macrophages.