Modulation of CD1d-restricted NKT cell responses by using N-acyl variants of α-galactosylceram ides

被引：292

作者：

Yu, KOA

Im, JS

Molano, A

Dutronc, Y

Illarionov, PA

Forestier, C

Fujiwara, N

Arias, I

Miyake, S

Yamamura, T

Chang, YT

Besra, GS

Porcelli, SA

机构：

[1] Albert Einstein Coll Med, Dept Microbiol & Immunol, Bronx, NY 10461 USA

[2] Univ Birmingham, Sch Biosci, Birmingham B15 2TT, W Midlands, England

[3] Natl Ctr Neurol & Psychiat, Natl Inst Neurosci, Dept Immunol, Tokyo 1878502, Japan

[4] NYU, Dept Chem, New York, NY 10003 USA

来源：

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA | 2005年 / 102卷 / 09期

关键词：

cytokines; inflammation; autoimmunity; immunoregulation;

D O I：

10.1073/pnas.0407488102

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

A form of alpha-galactosylceramide, KRN7000, activates CD1d-restricted Valpha14-invariant (Valpha14i) natural killer (NK) T cells and initiates multiple downstream immune reactions. We report that substituting the C26:0 N-acyl chain of KRN7000 with shorter, unsaturated fatty acids modifies the outcome of Valpha14i NKT cell activation. One analogue containing a diunsaturated C20 fatty acid (C20:2) potently induced a T helper type 2-biased cytokine response, with diminished IFN-gamma production and reduced Valpha14i NKT cell expansion. C20:2 also exhibited less stringent requirements for loading onto CD1d than KRN7000, suggesting a mechanism for the immunomodulatory properties of this lipid. The differential cellular response elicited by this class of Valpha14i NKT cell agonists may prove to be useful in immunotherapeutic applications.

引用

页码：3383 / 3388

页数：6

共 52 条

[1]

Behar SM, 1999, J IMMUNOL, V162, P161

[2] A thymic precursor to the NK T cell lineage [J].