Immune insufficiency during GVHD is due to defective antigen presentation within dendritic cell subsets

被引：39

作者：

Markey, Kate A. ^{[1
]}

Koyama, Motoko ^{[1
]}

Kuns, Rachel D. ^{[1
]}

Lineburg, Katie E. ^{[1
]}

Wilson, Yana A. ^{[1
]}

Olver, Stuart D. ^{[1
]}

Raffelt, Neil C. ^{[1
]}

Don, Alistair L. J. ^{[1
]}

Varelias, Antiopi ^{[1
]}

Robb, Renee J. ^{[1
,2
]}

Cheong, Melody ^{[1
]}

Engwerda, Christian R. ^{[3
]}

Steptoe, Raymond J. ^{[4
]}

Ramshaw, Hayley S. ^{[5
,6
]}

Lopez, Angel F. ^{[5
,6
]}

Vega-Ramos, Javier ^{[7
]}

Lew, Andrew M. ^{[8
]}

Villadangos, Jose A. ^{[7
]}

Hill, Geoffrey R. ^{[1
,9
]}

MacDonald, Kelli P. A. ^{[1
]}

机构：

[1] Queensland Inst Med Res, Bone Marrow Transplantat Lab, Brisbane, Qld 4006, Australia

[2] Univ Queensland, Sch Med, Herston, Qld, Australia

[3] Queensland Inst Med Res, Immunol & Infect Lab, Brisbane, Qld 4006, Australia

[4] Univ Queensland, Princess Alexandra Hosp, Diamantina Inst, Brisbane, Qld, Australia

[5] S Australian Pathol, Ctr Canc Biol, Adelaide, SA, Australia

[6] Univ Adelaide, Adelaide, SA, Australia

[7] Univ Melbourne, Fac Med Dent & Hlth Sci, Melbourne, Vic, Australia

[8] Walter & Eliza Hall Inst Med Res, Melbourne, Vic 3050, Australia

[9] Royal Brisbane & Womens Hosp, Dept Bone Marrow Transplantat, Brisbane, Qld, Australia

来源：

BLOOD | 2012年 / 119卷 / 24期

基金：

英国医学研究理事会;

关键词：

HOST-INDUCED IMMUNOSUPPRESSION; CD8(+) T-CELLS; IN-VIVO; CROSS-PRESENTATION; BETA-CHAIN; GRAFT; EXPRESSION; EFFECTOR; DISEASE; TRANSPLANTATION;

D O I：

10.1182/blood-2011-12-398164

中图分类号：

R5 [内科学];

学科分类号：

100201 [内科学];

摘要：

Alloreactivity after transplantation is associated with profound immune suppression, and consequent opportunistic infection results in high morbidity and mortality. This immune suppression is most profound during GVHD after bone marrow transplantation where an inflammatory cytokine storm dominates. Contrary to current dogma, which avers that this is a T-cell defect, we demonstrate that the impairment lies within conventional dendritic cells (cDCs). Significantly, exogenous antigens can only be presented by the CD8(-) cDC subset after bone marrow transplantation, and inflammation during GVHD specifically renders the MHC class II presentation pathway in this population incompetent. In contrast, both classic and cross-presentation within MHC class I remain largely intact. Importantly, this defect in antigen processing can be partially reversed by TNF inhibition or the adoptive transfer of donor cDCs generated in the absence of inflammation. (Blood. 2012; 119(24):5918-5930)

引用

页码：5918 / 5930

页数：13

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