Greifenberg Verena, Ribechini Eliana, Rössner Susanne, Lutz Manfred B
Department of Dermatology, University Hospital Erlangen, Erlangen, Germany.
Eur J Immunol. 2009 Oct;39(10):2865-76. doi: 10.1002/eji.200939486.
Myeloid-derived suppressor cells (MDSC) and DC are major controllers of immune responses against tumors or infections. However, it remains unclear how DC development and MDSC suppressor activity both generated from myeloid precursor cells are regulated. Here, we show that the combined treatment of BM-derived MDSC with LPS plus IFN-gamma inhibited the DC development but enhanced MDSC functions, such as NO release and T-cell suppression. This was not observed by the single treatments in vitro. In the spleens of healthy mice, we identified two Gr-1(low)CD11b(high)Ly-6C(high)SSC(low)Mo-MDSC and Gr-1(high)CD11b(low)PMN-MDSC populations with suppressive potential, whereas Gr-1(high)CD11b(high) neutrophils and Gr-1(low)CD11b(high)SSC(low) eosinophils were not suppressive. Injections of LPS plus IFN-gamma expanded these populations within the spleen but not LN leading to the block of the proliferation of CD8(+) T cells. At the same time, their capacity to develop into DC was impaired. Together, our data suggest that spleens of healthy mice contain two subsets of MDSC with suppressive potential. A two-signal-program through combined LPS and IFN-gamma treatment expands and fully activates MDSC in vitro and in vivo.
髓源性抑制细胞（MDSC）和树突状细胞（DC）是针对肿瘤或感染的免疫反应的主要调控者。然而，由髓系前体细胞产生的DC发育和MDSC抑制活性是如何被调控的仍不清楚。在此，我们表明，用脂多糖（LPS）加干扰素-γ联合处理骨髓来源的MDSC可抑制DC发育，但增强MDSC功能，如一氧化氮释放和T细胞抑制。体外单一处理未观察到这种情况。在健康小鼠的脾脏中，我们鉴定出两个具有抑制潜能的群体，即Gr-1（低）CD11b（高）Ly-6C（高）SSC（低）单核细胞源性MDSC和Gr-1（高）CD11b（低）多形核细胞源性MDSC，而Gr-1（高）CD11b（高）中性粒细胞和Gr-1（低）CD11b（高）SSC（低）嗜酸性粒细胞没有抑制作用。注射LPS加干扰素-γ可使脾脏内这些群体扩增，但淋巴结内不会，从而导致CD8(+)T细胞增殖受阻。同时，它们发育为DC的能力受损。总之，我们的数据表明健康小鼠的脾脏含有两个具有抑制潜能的MDSC亚群。通过联合LPS和干扰素-γ处理的双信号程序可在体外和体内扩增并完全激活MDSC。
