Dexamethasone promotes tolerance in vivo by enriching CD11clo CD40lo tolerogenic macrophages
| Autor: | Guoxing, Zheng, Shibo, Zhong, Yajun, Geng, Gnanasekar, Munirathinam, Isaac, Cha, Catherine, Reardon, Godfrey S, Getz, Nico, van Rooijen, Youmin, Kang, Bin, Wang, Aoshuang, Chen |
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| Rok vydání: | 2012 |
| Předmět: |
Mice
Inbred BALB C CD11 Antigens Macrophages Histocompatibility Antigens Class II Dendritic Cells T-Lymphocytes Regulatory Dexamethasone Interleukin-10 Mice Inbred C57BL Mice Cell Movement T-Lymphocyte Subsets Immune Tolerance Animals Hypersensitivity Delayed B7-2 Antigen CD40 Antigens Cells Cultured Immunosuppressive Agents |
| Zdroj: | European journal of immunology. 43(1) |
| ISSN: | 1521-4141 |
| Popis: | We previously showed that antigen immunization in the presence of the immunosuppressant dexamethasone (a strategy we termed "suppressed immunization") could tolerize established recall responses of T cells. However, the mechanism by which dexamethasone acts as a tolerogenic adjuvant has remained unclear. In the present study, we show that dexamethasone enriches CD11c(lo) CD40(lo) macrophages in a dose-dependent manner in the spleen and peripheral lymph nodes of mice by depleting all other CD11c(+) CD40(+) cells including dendritic cells. The enriched macrophages display a distinct MHC class II (MHC II)(lo) CD86(hi) phenotype. Upon activation by antigen in vivo, CD11c(lo) CD40(lo) macrophages upregulate IL-10, a classic marker for tolerogenic antigen-presenting cells, and elicit a serum IL-10 response. When presenting antigen in vivo, these cells do not elicit recall responses from memory T cells, but rather stimulate the expansion of antigen-specific regulatory T cells. Moreover, the depletion of CD11c(lo) CD40(lo) macrophages during suppressed immunization diminishes the tolerogenic efficacy of the treatment. These results indicate that dexamethasone acts as a tolerogenic adjuvant partly by enriching the CD11c(lo) CD40(lo) tolerogenic macrophages. |
| Databáze: | OpenAIRE |
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