Donor B Cells in Transplants Augment Clonal Expansion and Survival of Pathogenic CD4+ T Cells That Mediate Autoimmune-like Chronic Graft-versus-Host Disease

被引：80

作者：

Young, James S. ^{[1
,2
,3
]}

Wu, Tao ^{[1
,3
,4
]}

Chen, Yuhong ^{[1
,3
,5
]}

Zhao, Dongchang ^{[1
,3
]}

Liu, Hongjun ^{[1
,3
]}

Yi, Tangsheng ^{[1
,2
,3
]}

Johnston, Heather ^{[1
,2
,3
]}

Racine, Jeremy ^{[1
,2
,3
]}

Li, Xiaofan ^{[1
,3
,6
]}

Wang, Audrey ^{[7
]}

Todorov, Ivan ^{[1
]}

Zeng, Defu ^{[1
,2
,3
]}

机构：

[1] City Hope Natl Med Ctr, Beckman Res Inst, Dept Diabet Endocrinol, Duarte, CA 91010 USA

[2] City Hope Natl Med Ctr, Irell & Manella Grad Sch Biol Sci, Duarte, CA 91010 USA

[3] City Hope Natl Med Ctr, Beckman Res Inst, Dept Hematol & Hematopoiet Cell Transplantat, Duarte, CA 91010 USA

[4] Second Mil Med Univ, Changhai Hosp, Dept Hematol, Shanghai 200433, Peoples R China

[5] Peking Univ, Peoples Hosp, Inst Hematol, Beijing 100044, Peoples R China

[6] Fujian Med Univ, Union Hosp, Fujian Inst Hematol, Dept Hematol, Fuzhou 350001, Peoples R China

[7] City Hope Natl Med Ctr, Eugene & Ruth Roberts Summer Student Acad, Duarte, CA 91010 USA

来源：

JOURNAL OF IMMUNOLOGY | 2012年 / 189卷 / 01期

关键词：

ANTIGEN-PRESENTING CELLS; CHRONIC GVHD; RITUXIMAB; RECONSTITUTION; REQUIREMENT; MOLECULES; DEPLETION; BLOOD; MICE;

D O I：

10.4049/jimmunol.1200677

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

We reported that both donor CD4(+) T and B cells in transplants were required for induction of an autoimmune-like chronic graft-versus-host disease (cGVHD) in a murine model of DBA/2 donor to BALB/c recipient, but mechanisms whereby donor B cells augment cGVHD pathogenesis remain unknown. In this study, we report that, although donor B cells have little impact on acute GVHD severity, they play an important role in augmenting the persistence of tissue damage in the acute and chronic GVHD overlapping target organs (i.e., skin and lung); they also markedly augment damage in a prototypical cGVHD target organ, the salivary gland. During cGVHD pathogenesis, donor B cells are activated by donor CD4(+) T cells to upregulate MHC II and costimulatory molecules. Acting as efficient APCs, donor B cells augment donor CD4(+) T clonal expansion, autoreactivity, IL-7Ra expression, and survival. These qualitative changes markedly augment donor CD4(+) T cells' capacity in mediating autoimmune-like cGVHD, so that they mediate disease in the absence of donor B cells in secondary recipients. Therefore, a major mechanism whereby donor B cells augment cGVHD is through augmenting the clonal expansion, differentiation, and survival of pathogenic CD4(+) T cells. The Journal of Immunology, 2012, 189: 222-233.

引用

页码：222 / 233

页数：12