Complement regulator CD46 temporally regulates cytokine production by conventional and unconventional T cells

被引：233

作者：

Cardone, John ^{[1
]}

Le Friec, Gaelle ^{[1
]}

Vantourout, Pierre ^{[2
,3
]}

Roberts, Andrew ^{[2
,3
]}

Fuchs, Anja ^{[4
]}

Jackson, Ian ^{[1
,5
]}

Suddason, Tesha ^{[1
,5
]}

Lord, Graham ^{[1
,5
]}

Atkinson, John P. ^{[6
]}

Cope, Andrew ^{[5
,7
]}

Hayday, Adrian ^{[1
,2
,3
,5
]}

Kemper, Claudia ^{[1
]}

机构：

[1] Guys Hosp, Div Immunol Infect & Inflammatory Dis, Kings Coll London, Med Res Council,Ctr Transplantat, London SE1 9RT, England

[2] Canc Res UK, London Res Inst, London, England

[3] Guys Hosp, Peter Gorer Dept Immunobiol, Kings Coll London, London SE1 9RT, England

[4] Washington Univ, Sch Med, Div Immunol & Pathol, Dept Med, St Louis, MO USA

[5] Guys Hosp, Kings Hlth Partners, Biomed Res Ctr, London SE1 9RT, England

[6] Washington Univ, Sch Med, Div Rheumatol, Dept Med, St Louis, MO USA

[7] Kings Coll London, Acad Dept Rheumatol, London WC2R 2LS, England

来源：

NATURE IMMUNOLOGY | 2010年 / 11卷 / 09期

基金：

英国惠康基金; 英国医学研究理事会; 美国国家卫生研究院;

关键词：

COFACTOR PROTEIN MCP; INTERFERON-GAMMA; ADAPTIVE IMMUNITY; INNATE IMMUNITY; IFN-GAMMA; IN-VIVO; INTERLEUKIN-10; ACTIVATION; IL-10; LYMPHOCYTES;

D O I：

10.1038/ni.1917

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

In this study we demonstrate a new form of immunoregulation: engagement on CD4(+) T cells of the complement regulator CD46 promoted the effector potential of T helper type 1 cells (T(H)1 cells), but as interleukin 2 (IL-2) accumulated, it switched cells toward a regulatory phenotype, attenuating IL-2 production via the transcriptional regulator ICER/CREM and upregulating IL-10 after interaction of the CD46 tail with the serine-threonine kinase SPAK. Activated CD4(+) T cells produced CD46 ligands, and blocking CD46 inhibited IL-10 production. Furthermore, CD4(+) T cells in rheumatoid arthritis failed to switch, consequently producing excessive interferon-gamma (IFN-gamma). Finally, gamma delta T cells, which rarely produce IL-10, expressed an alternative CD46 isoform and were unable to switch. Nonetheless, coengagement of T cell antigen receptor (TCR) gamma delta and CD46 suppressed effector cytokine production, establishing that CD46 uses distinct mechanisms to regulate different T cell subsets during an immune response.

引用

页码：862 / U123

页数：11

共 50 条

[1] CD4+CD25-Foxp3- Th1 cells are the source of IL-10-mediated immune suppression in chronic cutaneous leishmaniasis [J].