TY - JOUR
T1 - Development and maturation of invariant NKT cells in the presence of lysosomal engulfment
AU - Plati, Tiziana
AU - Visigalli, Ilaria
AU - Capotondo, Alessia
AU - Buono, Mario
AU - Naldini, Luigi
AU - Cosma, Maria Pia
AU - Biffi, Alessandra
PY - 2009/10
Y1 - 2009/10
N2 - A defect in invariant NKT (iNKT) cell selection was hypothesized in lysosomal storage disorders (LSD). Accumulation of glycosphingolipids (GSL) in LSD could influence lipid loading and/or presentation causing entrapment of endogenous ligand(s) within storage bodies or competition of the selecting ligand(s) by stored lipids for CD1d binding. However, when we analyzed the iNKT cell compartment in newly tested LSD animal models that accumulate GSL, glycoaminoglycans or both, we observed a defective iNKT cell selection only in animals affected by multiple sulfatase deficiency, in which a generalized aberrant T-cell development, rather than a pure iNKT defect, was present. Mice with single lysosomal enzyme deficiencies had normal iNKT cell development. Thus, GSL/glycoaminoglycans storage and lysosomal engulfment are not sufficient for affecting iNKT cell development. Rather, lipid ligand(s) or storage compounds, which are affected in those LSD lacking mature iNKT cells, might indeed be relevant for iNKT cell selection.
AB - A defect in invariant NKT (iNKT) cell selection was hypothesized in lysosomal storage disorders (LSD). Accumulation of glycosphingolipids (GSL) in LSD could influence lipid loading and/or presentation causing entrapment of endogenous ligand(s) within storage bodies or competition of the selecting ligand(s) by stored lipids for CD1d binding. However, when we analyzed the iNKT cell compartment in newly tested LSD animal models that accumulate GSL, glycoaminoglycans or both, we observed a defective iNKT cell selection only in animals affected by multiple sulfatase deficiency, in which a generalized aberrant T-cell development, rather than a pure iNKT defect, was present. Mice with single lysosomal enzyme deficiencies had normal iNKT cell development. Thus, GSL/glycoaminoglycans storage and lysosomal engulfment are not sufficient for affecting iNKT cell development. Rather, lipid ligand(s) or storage compounds, which are affected in those LSD lacking mature iNKT cells, might indeed be relevant for iNKT cell selection.
KW - Invariant NKT cells
KW - Lysosomal storage disorders
KW - Selecting ligand
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U2 - 10.1002/eji.200939639
DO - 10.1002/eji.200939639
M3 - Article
C2 - 19637231
AN - SCOPUS:70350553839
VL - 39
SP - 2748
EP - 2754
JO - European Journal of Immunology
JF - European Journal of Immunology
SN - 0014-2980
IS - 10
ER -