A CD2 high-expressing stress-resistant human plasmacytoid dendritic-cell subset

被引：30

作者：

Bryant, Christian ^{[1
,2
,3
]}

Fromm, Phillip D. ^{[1
,2
]}

Kupresanin, Fiona ^{[1
]}

Clark, Georgina ^{[1
,2
]}

Lee, Kenneth ^{[2
,4
]}

Clarke, Candice ^{[4
]}

Silveira, Pablo A. ^{[1
,2
]}

Suen, Hayley ^{[3
]}

Brown, Ross ^{[3
]}

Newman, Elizabeth ^{[5
]}

Cunningham, Ilona ^{[5
]}

Ho, P. Joy ^{[3
]}

Gibson, John ^{[3
]}

Bradstock, Kenneth ^{[1
,6
]}

Joshua, Douglas ^{[3
]}

Hart, Derek N. J. ^{[1
,2
,3
,5
]}

机构：

[1] Concord Repatriat Gen Hosp, ANZAC Res Inst, Dendrit Cell Res, Gate 3,Hosp Rd, Sydney, NSW 2139, Australia

[2] Univ Sydney, Concord Clin Sch, Sydney, NSW 2006, Australia

[3] Royal Prince Alfred Hosp, Dept Haematol, Sydney, NSW, Australia

[4] Concord Repatriat Gen Hosp, Dept Anat Pathol, Gate 3,Hosp Rd, Sydney, NSW 2139, Australia

[5] Concord Hosp, Dept Haematol, Sydney, NSW, Australia

[6] Westmead Hosp, Blood & Bone Marrow Transplant Serv, Sydney, NSW, Australia

来源：

IMMUNOLOGY AND CELL BIOLOGY | 2016年 / 94卷 / 05期

基金：

英国医学研究理事会;

关键词：

T-CELLS; PREDENDRITIC CELLS; MULTIPLE-MYELOMA; FACTOR E2-2; APOPTOSIS; MONOCYTES; PHENOTYPE; SURVIVAL; DCS; GLUCOCORTICOIDS;

D O I：

10.1038/icb.2015.116

中图分类号：

Q2 [细胞生物学];

学科分类号：

071013 [干细胞生物学];

摘要：

Human plasmacytoid dendritic cells (pDCs) were considered to be a phenotypically and functionally homogeneous cell population; however, recent analyses indicate potential heterogeneity. This is of major interest, given their importance in the induction of anti-viral responses and their role in creating immunologically permissive environments for human malignancies. For this reason, we investigated the possible presence of human pDC subsets in blood and bone marrow, using unbiased cell phenotype clustering and functional studies. This defined two major functionally distinct human pDC subsets, distinguished by differential expression of CD2. The CD2(hi) and CD2(Io) pDCs represent discontinuous subsets, each with hallmark pDC functionality, including interferon-alpha production. The rarer CD2(hi) pDC subset demonstrated a significant survival advantage over CD2(Io) pDC during stress and upon exposure to glucocorticoids (GCs), which was associated with higher expression of the anti-apoptotic molecule BCL2. The differential sensitivity of these two human pDC subsets to GCs is demonstrated in vivo by a relative increase in CD2(hi) pDC in multiple myeloma patients treated with GCs. Hence, the selective apoptosis of CD2(Io) pDC during stress represents a novel mechanism for the control of innate responses.

引用

页码：447 / 457

页数：11

共 57 条

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CD2 rescues T cells from T-cell receptor CD3 apoptosis: A role for the Fas/Fas-L system [J].