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Preclinical and Clinical Development of Synthetic iNKT-Cell Glycolipid Agonists as Vaccine Adjuvants

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Novel Immune Potentiators and Delivery Technologies for Next Generation Vaccines

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Abstract

NKT cells are a separate lineage of T lymphocytes that co-express receptors for the T-cell and natural killer (NK) cell lineages. Most NKT cells express a semi-invariant T-cell receptor (TCR), Vα14-Jα18 paired with Vβ8.2, Vβ7 or Vβ2 in mice and Vα24-Jα18/Vβ11 in human [1–5]. These cells are referred to as iNKT cells type I NKT cells, or NKT cells, in contrast to type II NKT cells comprising the remaining NKT cells expressing non-invariant TCR [6]. These cells share phenotypic and functional characteristics of T and NK cells. The phenotype of NKT cells expresses a T-cell receptor αβ (TCRαβ), the CD4 or the CD8 co-receptor or neither of them [double-negative (DN) phenotype], the NK1.1 marker, and some Ly49 receptors [7–10]. Emerging evidence indicates that CD4+ and CD4− iNKT cell subsets are functionally distinct [11–13]. The distribution of iNKT cells has been well studied in mice, and less well in human. Murine iNKT cells represent approximately 0.5 % of the T-cell population in the blood and peripheral lymph nodes (LN), and up to 30 % of T cells in the liver, and this population appears to be times less frequent in humans. However, high and low expressers are found in humans and mice [14–17].

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  1. Wittycell SAS, 4 Rue Pierre Fontaine, 91000, Evry, France

    Josianne Nitcheu, Sandrine Crabe & Vincent Serra

  2. St George’s University of London, Cranmer Terrace, London, SW17 0RE, UK

    Gwyn Davies

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  1. Josianne Nitcheu
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Correspondence to Josianne Nitcheu .

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    Manmohan Singh

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Nitcheu, J., Crabe, S., Davies, G., Serra, V. (2013). Preclinical and Clinical Development of Synthetic iNKT-Cell Glycolipid Agonists as Vaccine Adjuvants. In: Singh, M. (eds) Novel Immune Potentiators and Delivery Technologies for Next Generation Vaccines. Springer, Boston, MA. https://doi.org/10.1007/978-1-4614-5380-2_2

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