DX5+NKT cells display phenotypical and functional differences between spleen and liver as well as NK1.1-Balb/c and NK1.1+ C57Bl/6 mice

In the spleen 34% of DX5+NKT cells expressed CD62L and they up-regulated the functional receptors CD154 as well as CD178 upon activation. In contrast, only a few liver DX5+NKT cells expressed CD62L, and they did not up-regulate CD154 upon activation. A further difference between spleen and liver subsets was observed in cytokine production. Spleen DX5+NKT cells produced more Th1 cytokines including IL-2, IFN-γ and TNF-α, while liver DX5+NKT cells secreted more Th2 cytokines (e.g. IL-4) and even the Th17 cytokine, IL-17a. Furthermore, we found inter-strain differences. In NK1.1+ C57Bl/6 mice DX5+NKT cells represented a distinct T cell population expressing less CD4 and more CD8. Accordingly, these cells showed a CD178 and Th2-type functional capacity upon activation.These results show that DX5+NKT cells are a heterogeneous population, depending on the dedicated organ and mouse strain, that has diverse functional capacity.Natural killer T (NKT) cells represent a small but important subset of T lymphocytes with characteristics of both T and NK cells. They have potent immunoregulatory function that reportedly can promote cell-mediated immunity to tumors and infectious organisms and, paradoxically, suppress cell-mediated immunity associated with autoimmune disease and allograft rejection [1]. In mice, these cells express NK cell markers such as NK1.1 and CD94, as well as T-cell receptors (TCR) α/β with a restricted repertoire [2,3]. The invariant T cell receptor α chain Vα14-Jα18 with a conserved CDR3 region is associated with Vβ8.2, Vβ7 or Vβ2 gene segments [3,4].In contrast to conventional T-lymphocytes, the TCR of NKT cells does not interact with antigens presented by classical major histocompatibility complex (MHC)-encoded class I or II molecules. Instead, their TCR recognizes glycolipids presented by CD1d, which is a MHC class-I-like glycoprotein that belongs to a group of CD1 molecules associated with β2-microglobulin [5-7]. CD1d is known to present lipids including