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Engagement of glycosylphosphatidylinositol‐anchored proteins results in enhanced mouse and human invariant natural killer T cell responses
Author(s) -
Mannik Lisa A.,
ChinYee Ian,
Sharif Shayan,
Van Kaer Luc,
Delovitch Terry L.,
Haeryfar S. M. Mansour
Publication year - 2011
Publication title -
immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.297
H-Index - 133
eISSN - 1365-2567
pISSN - 0019-2805
DOI - 10.1111/j.1365-2567.2010.03369.x
Subject(s) - cd1d , microbiology and biotechnology , biology , natural killer t cell , cytokine , secretion , cd8 , antigen , immunology , biochemistry
Summary Invariant natural killer T ( i NKT) cells are a small subset of lymphocytes that recognize glycolipid antigens in the context of CD1d and consequently produce large quantities of pro‐inflammatory and/or anti‐inflammatory cytokines. Several transmembrane glycoproteins have been implicated in the co‐stimulation of i NKT cell responses. However, whether glycosylphosphatidylinositol (GPI)‐anchored proteins can function in this capacity is not known. Here, we demonstrate that antibody‐mediated cross‐linking of the prototype mouse GPI‐anchored protein Thy‐1 (CD90) on the surface of a double‐negative (CD4 − CD8 − ) i NKT cell line leads to cytokine production at both the mRNA and protein levels. In addition, Thy‐1 triggering enhanced cytokine secretion by i NKT cells that were concomitantly stimulated with α‐galactosylceramide (αGC), consistent with a co‐stimulatory role for Thy‐1 in i NKT cell activation. This was also evident when a CD4 + mouse i NKT cell line or primary hepatic NKT cells were stimulated with αGC and/or anti‐Thy‐1 antibody. Cross‐linking Ly‐6A/E, another GPI‐anchored protein, could also boost cytokine secretion by αGC‐stimulated i NKT cells, suggesting that the observed effects reflect a general property of GPI‐anchored proteins. To extend these results from mouse to human cells, we focused on CD55, a GPI‐anchored protein that, unlike Thy‐1, is expressed on human i NKT cells. Cross‐linking CD55 augmented αGC‐induced i NKT cell responses as judged by more vigorous proliferation and higher CD69 expression. Collectively, these findings demonstrate for the first time that GPI‐anchored proteins are able to co‐stimulate CD1d‐restricted, glycolipid‐reactive i NKT cells in both mice and humans.