Dexamethasone promotes tolerance in vivo by enriching CD 11c super(lo) CD 40 super(lo) tolerogenic macrophages

• Published in: European journal of immunology Vol. 43; no. 1; pp. 219 - 227
• Main Authors: Zheng, Guoxing, Zhong, Shibo, Geng, Yajun, Munirathinam, Gnanasekar, Cha, Isaac, Reardon, Catherine, Getz, Godfrey S, van Rooijen, Nico, Kang, Youmin, Wang, Bin, Chen, Aoshuang
• Format: Journal Article
• Language: English
• Published: 01.01.2013
• ISSN: 0014-2980; 1521-4141
• DOI: 10.1002/eji.201242468

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 CD 11c super(lo) CD 40 super(lo) macrophages in a dose-dependent manner in the spleen and peripheral lymph nodes of mice by depleting all other CD 11c super(+) CD 40 super(+) cells including dendritic cells. The enriched macrophages display a distinct MHC class II ( MHC II) super(lo) CD 86 super(hi) phenotype. Upon activation by antigen in vivo, CD 11c super(lo) CD 40 super(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 CD 11c super(lo) CD 40 super(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 CD 11c super(lo) CD 40 super(lo) tolerogenic macrophages.