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- Title
Ganglioside-exposed dendritic cells inhibit T-cell effector function by promoting regulatory cell activity.
- Authors
Jales, Alessandra; Falahati, Rustom; Mari, Elisabeth; Stemmy, Erik J; Shen, Weiping; Southammakosane, Cathy; Herzog, Dallen; Ladisch, Stephan; Leitenberg, David
- Abstract
Tumour pathogenesis is characterized by an immunosuppressive microenvironment that limits the development of effective tumour-specific immune responses. This is in part the result of tumour-dependent recruitment and activation of regulatory cells, such as myeloid-derived suppressor cells and regulatory T cells in the tumour microenvironment and draining lymph nodes. Shedding of gangliosides by tumour cells has immunomodulatory properties, suggesting that gangliosides may be a critical factor in initiating an immunosuppressive microenvironment. To better define the immunomodulatory properties of gangliosides on antigen-specific T-cell activation and development we have developed an in vitro system using ganglioside-treated murine bone-marrow-derived dendritic cells to prime and activate antigen-specific CD4(+) T cells from AND T-cell receptor transgenic mice. Using this system, ganglioside treatment promotes the development of a dendritic cell population characterized by decreased CD86 (B7-2) expression, and decreased interleukin-12 and interleukin-6 production. When these cells are used as antigen-presenting cells, CD4 T cells are primed to proliferate normally, but have a defect in T helper (Th) effector cell development. This defect in Th effector cell responses is associated with the development of regulatory T-cell activity that can suppress the activation of previously primed Th effector cells in a contact-dependent manner. In total, these data suggest that ganglioside-exposed dendritic cells promote regulatory T-cell activity that may have long-lasting effects on the development of tumour-specific immune responses.
- Publication
Immunology, 2011, Vol 132, Issue 1, p134
- ISSN
1365-2567
- Publication type
Journal Article
- DOI
10.1111/j.1365-2567.2010.03348.x