Function of CD4+CD3- cells in relation to B- and T-zone stroma in spleen

被引:71
作者
Kim, Mi-Yeon [1 ]
McConnell, Fiona M. [1 ]
Gaspal, Fabrina M. C. [1 ]
White, Andrea [1 ]
Glanville, Stephanie H. [1 ]
Bekiaris, Vasilios [1 ]
Walker, Lucy S. K. [1 ]
Caamano, Jorge [1 ]
Jenkinson, Eric [1 ]
Anderson, Graham [1 ]
Lane, Peter J. L. [1 ]
机构
[1] Univ Birmingham Sch Med, MRC, Ctr Immune Regulat, Biomed Res Inst, Birmingham B15 2TT, W Midlands, England
基金
英国医学研究理事会;
关键词
D O I
10.1182/blood-2006-04-018465
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Lymphocytes from lymphotoxin (LT) alpha-deficient mice, which lack segregation of their B- and T-cell areas, acquire normal organization following adoptive transfer into RAG-deficient recipients, identifying a non-B non-T cell in the segregation process. Here we show that a CD4(+)CD3(-) accessory cell is tightly associated with discrete VCAM-1-expressing stromal cells in B- and T-cell areas of the mouse spleen. CD4(+)CD3(-) cells express high levels of LT alpha, LTP beta and tumor necrosis factor (TNF)alpha, which are the ligands for the LT beta receptor and TNFR1 expressed by stromal cells. The expression of these ligands is functional, as transferring CD4(+)CD3(-) cells derived from either embryonic or adult tissues into LT alpha-deficient mice organizes B/T segregation and up-regulates CCL21 protein expression in areas where T cells are segregated from B cells. We propose that the function of CD4(+)CD3(-) cells is to form a link between primed CD4 T cells and the underlying stromal elements, creating distinct microenvironments in which they enable effector responses.
引用
收藏
页码:1602 / 1610
页数:9
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