TY - JOUR
T1 - Quantitative and qualitative differences in the in vivo response of NKT cells to distinct α- and β-anomeric glycolipids
AU - Parekh, Vrajesh V.
AU - Singh, Avneesh K.
AU - Wilson, Michael T.
AU - Olivares-Villagómez, Danyvid
AU - Bezbradica, Jelena S.
AU - Inazawa, Hiroko
AU - Ehara, Hiromi
AU - Sakai, Teruyuki
AU - Serizawa, Isao
AU - Wu, Lan
AU - Wang, Chyung Ru
AU - Joyce, Sebastian
AU - Van Kaer, Luc
PY - 2004/9/15
Y1 - 2004/9/15
N2 - NKT cells represent a unique subset of immunoregulatory T cells that recognize glycolipid Ags presented by the MHC class I-like molecule CD1d. Because of their immunoregulatory properties, NKT cells are attractive targets for the development of immunotherapies. The prototypical NKT cell ligand α-galactosylceramide (α-GalCer), originally isolated from a marine sponge, has potent immunomodulatory activities in mice, demonstrating therapeutic efficacy against metastatic tumors, infections, and autoimmune diseases, but also has a number of adverse side effects. In vivo administration of α-GalCer to mice results in the rapid activation of NKT cells, which is characterized by cytokine secretion, surface receptor down-regulation, expansion, and secondary activation of a variety of innate and adaptive immune system cells. In this study, we have evaluated the in vivo immune response of mice to a set of structural analogues of α-GalCer. Our results show that, contrary to current thinking, β-anomeric GalCer can induce CD1d-dependent biological activities in mice, albeit at lower potency than α-anomeric GalCer. In addition, we show that the response of NKT cells to distinct GalCer differs not only quantitatively, but also qualitatively. These findings indicate that NKT cells can fine-tune their immune responses to distinct glycolipid Ags in vivo, a property that may be exploited for the development of effective and safe NKT cell-based immunotherapies.
AB - NKT cells represent a unique subset of immunoregulatory T cells that recognize glycolipid Ags presented by the MHC class I-like molecule CD1d. Because of their immunoregulatory properties, NKT cells are attractive targets for the development of immunotherapies. The prototypical NKT cell ligand α-galactosylceramide (α-GalCer), originally isolated from a marine sponge, has potent immunomodulatory activities in mice, demonstrating therapeutic efficacy against metastatic tumors, infections, and autoimmune diseases, but also has a number of adverse side effects. In vivo administration of α-GalCer to mice results in the rapid activation of NKT cells, which is characterized by cytokine secretion, surface receptor down-regulation, expansion, and secondary activation of a variety of innate and adaptive immune system cells. In this study, we have evaluated the in vivo immune response of mice to a set of structural analogues of α-GalCer. Our results show that, contrary to current thinking, β-anomeric GalCer can induce CD1d-dependent biological activities in mice, albeit at lower potency than α-anomeric GalCer. In addition, we show that the response of NKT cells to distinct GalCer differs not only quantitatively, but also qualitatively. These findings indicate that NKT cells can fine-tune their immune responses to distinct glycolipid Ags in vivo, a property that may be exploited for the development of effective and safe NKT cell-based immunotherapies.
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U2 - 10.4049/jimmunol.173.6.3693
DO - 10.4049/jimmunol.173.6.3693
M3 - Article
C2 - 15356115
AN - SCOPUS:4644221871
SN - 0022-1767
VL - 173
SP - 3693
EP - 3706
JO - Journal of Immunology
JF - Journal of Immunology
IS - 6
ER -