Neonatal and adult recent thymic emigrants produce IL-8 and express complement receptors CR1 and CR2

被引:52
作者
Pekalski, Marcin L. [1 ,2 ]
Garcia, Arcadio Rubio [1 ,2 ]
Ferreira, Ricardo C. [1 ,2 ]
Rainbow, Daniel B. [1 ,2 ]
Smyth, Deborah J. [2 ]
Mashar, Meghavi [2 ]
Brady, Jane [2 ]
Savinykh, Natalia [2 ]
Dopico, Xaquin Castro [2 ]
Mahmood, Sumiyya [2 ]
Duley, Simon [2 ]
Stevens, Helen E. [2 ]
Walker, Neil M. [2 ]
Cutler, Antony J. [1 ,2 ]
Waldron-Lynch, Frank [2 ,9 ,10 ]
Dunger, David B. [3 ]
Shannon-Lowe, Claire [4 ,5 ]
Coles, Alasdair J. [6 ]
Jones, Joanne L. [6 ]
Wallace, Chris [2 ,7 ,8 ]
Todd, John A. [1 ,2 ]
Wicker, Linda S. [1 ,2 ]
机构
[1] Univ Oxford, Oxford Biomed Res Ctr, NIHR,JDRF Wellcome Trust Diabet & Inflammat Lab, Nuffield Dept Med,Wellcome Trust Ctr Human Genet, Oxford, England
[2] Univ Cambridge, NIHR Cambridge Biomed Res Ctr, Cambridge Inst Med Res, Wellcome Trust,JDRF Wellcome Trust Diabet & Infla, MRC Bldg, Cambridge, England
[3] Univ Cambridge, NIHR Cambridge Comprehens Biomed Res Ctr, MRC Inst Metab Sci, MRL Wellcome Trust,Dept Paediat, Cambridge, England
[4] Univ Birmingham, Inst Immunol & Immunotherapy, Birmingham, W Midlands, England
[5] Univ Birmingham, Ctr Human Virol, Birmingham, W Midlands, England
[6] Univ Cambridge, Dept Clin Neurosci, Cambridge, England
[7] Univ Cambridge, Addenbrookes Hosp, Dept Med, Cambridge, England
[8] Cambridge Inst Publ Hlth, MRC Biostat Unit, Cambridge Biomed Campus, Cambridge, England
[9] Univ Cambridge, Addenbrookes Hosp, NIHR Cambridge Biomed Res Ctr, Dept Med,Expt Med & Immunotherapeut, Cambridge, England
[10] Univ Cambridge, Cambridge Univ Hosp NHS Fdn Trust, NIHR Cambridge Clin Trials Unit, Cambridge Biomed Campus, Cambridge, England
基金
英国惠康基金;
关键词
CD4(+) T-CELLS; INFECTION; MAINTENANCE; ACTIVATION; IMMUNITY; DIFFERENTIATION; AUTOIMMUNITY; SUBSETS; CD21;
D O I
10.1172/jci.insight.93739
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
1001 ;
摘要
The maintenance of peripheral naive T lymphocytes in humans is dependent on their homeostatic division, not continuing emigration from the thymus, which undergoes involution with age. However, postthymic maintenance of naive T cells is still poorly understood. Previously we reported that recent thymic emigrants (RTEs) are contained in CD31(+)CD25(-) naive T cells as defined by their levels of signal joint T cell receptor rearrangement excision circles (sjTRECs). Here, by differential gene expression analysis followed by protein expression and functional studies, we define that the naive T cells having divided the least since thymic emigration express complement receptors (CR1 and CR2) known to bind complement C3b- and C3d-decorated microbial products and, following activation, produce IL-8 (CXCL8), a major chemoattractant for neutrophils in bacterial defense. We also observed an IL-8-producing memory T cell subpopulation coexpressing CR1 and CR2 and with a gene expression signature resembling that of RTEs. The functions of CR1 and CR2 on T cells remain to be determined, but we note that CR2 is the receptor for Epstein-Barr virus, which is a cause of T cell lymphomas and a candidate environmental factor in autoimmune disease.
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页数:16
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