Immunotherapeutic potential for ceramide-based activators of iNKT cells

被引：84

作者：

Berkers, CR ^{[1
]}

Ovaa, H ^{[1
]}

机构：

[1] Netherlands Canc Inst, Div Cellular Biochem, NL-1066 CX Amsterdam, Netherlands

来源：

TRENDS IN PHARMACOLOGICAL SCIENCES | 2005年 / 26卷 / 05期

关键词：

D O I：

10.1016/j.tips.2005.03.005

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

Invariant natural killer T (iNKT) cells are a subpopulation of T cells that are reactive with glycolipids that are bound by CD1d antigen-presenting molecules. alpha-Galactosylceramide (alpha-GalCer) is a synthetic glycolipid that is a potential treatment for several autoimmune diseases, infectious diseases and cancer. Its therapeutic effect can be traced back to its ability to bind CD1d and activate iNKT cells, which results in the production of T helper I (Th1) and Th2 cytokines. However, the effectiveness of alpha-GalCer therapy is limited by the opposing actions of Th1 and Th2 cytokines. The alpha-GalCer analogs OCH and the recently designed and synthesized C-glycosidic alpha-GalCer selectively activate one of two types of cytokine profiles, possibly because either reduced or enhanced overall stability of the CD1d-glycolipid-T-cell-receptor complex leads to a higher potency in vivo, compared with the parent compound. These discoveries boost the potential of glycolipid-based therapies.

引用

页码：252 / 257

页数：6

共 55 条

[1] A subset of liver NK T cells is activated during Leishmania donovani infection by CD1d-bound lipophosphoglycan [J].

Amprey, JL ;

Im, JS ;

Turco, SJ ;

Murray, HW ;

Illarionov, PA ;

Besra, GS ;

Porcelli, SA ;

Späth, GF .

JOURNAL OF EXPERIMENTAL MEDICINE, 2004, 200 (07) :895-904

[2] CD1: Antigen presentation and T cell function [J].

Brigl, M ;

Brenner, MB .

ANNUAL REVIEW OF IMMUNOLOGY, 2004, 22 :817-890

[3] The paradox of immune molecular recognition of α-galactosylceramide:: Low affinity, low specificity for CD1d, high affinity for αβ TCRs [J].

Cantu, C ;

Benlagha, K ;

Savage, PB ;

Bendelac, A ;

Teyton, L .

JOURNAL OF IMMUNOLOGY, 2003, 170 (09) :4673-4682

[4] PEPTIDE BINDING AND PRESENTATION BY MOUSE CD1 [J].

CASTANO, AR ;

TANGRI, S ;

MILLER, JEW ;

HOLCOMBE, HR ;

JACKSON, MR ;

HUSE, WD ;

KRONENBERG, M ;

PETERSON, PA .

SCIENCE, 1995, 269 (5221) :223-226

[5] Efficient synthesis of α-C-galactosyl ceramide immunostimulants:: Use of ethylene-promoted olefin cross-metathesis [J].

Chen, GW ;

Schmieg, J ;

Tsuji, M ;

Franck, RW .

ORGANIC LETTERS, 2004, 6 (22) :4077-4080

[6] Suppression of collagen-induced arthritis by natural killer T cell activation with OCK a sphingosine-truncated analog of α-galactosylceramide [J].

Chiba, A ;

Oki, S ;

Miyamoto, K ;

Hashimoto, H ;

Yamamura, T ;

Miyake, S .

ARTHRITIS AND RHEUMATISM, 2004, 50 (01) :305-313

[7] Immunomodulating glycosphingolipids:: an efficient synthesis of a 2′-deoxy-α-galactosyl-GSL [J].

Costantino, V ;

Fattorusso, E ;

Imperatore, C ;

Mangoni, A .

TETRAHEDRON, 2002, 58 (02) :369-375

[8] Glycolipid antigen drives rapid expansion and sustained cytokine production by NK T cells [J].

Crowe, NY ;

Uldrich, AP ;

Kyparissoudis, K ;

Hammond, KJL ;

Hayakawa, Y ;

Sidobre, S ;

Keating, R ;

Kronenberg, M ;

Smyth, MJ ;

Godfrey, DI .

JOURNAL OF IMMUNOLOGY, 2003, 171 (08) :4020-4027

[9] Evolutionary constraints on CD1 structure: insights from comparative genomic analysis [J].

Dascher, CC ;

Brenner, MB .

TRENDS IN IMMUNOLOGY, 2003, 24 (08) :412-418

[10] Mycobacterial phosphatidylinositol mannoside is a natural antigen for old-restricted T cells [J].

Fischer, K ;

Scotet, E ;

Niemeyer, M ;

Koebernick, H ;

Zerrahn, J ;

Maillet, S ;

Hurwitz, R ;

Kursar, M ;

Bonneville, M ;

Kaufmann, SHE ;

Schaible, UE .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2004, 101 (29) :10685-10690

← 1 2 3 4 5 6 →