Detection of Autoreactive Type II NKT Cells: A Pilot Study of Comparison Between Healthy Individuals and Patients with Vasculitis

Abstract

NKT cells are defined as T cells that recognize hydrophobic antigens presented by class I MHC-like molecules, including CD1d. Among CD1d-restricted NKT cells, type I and type II subsets have been noted. CD1d-restricted type I NKT cells are regarded as proinflammatory cells in general. On the contrary, accumulated evidence has demonstrated an anti-inflammatory property of CD1d-restricted type II NKT cells. In our earlier study using a rat model with vasculitis, we demonstrated the pro-inflammatory function of CD1d-restricted type II NKT cells and identified that one such cell recognized P 518-532 of rat sterol carrier protein 2 (rSCP2 518-532 ), which appeared on vascular endothelial cells presented by CD1d. Based on this evidence, we attempted to detect human CD1d-restricted type II NKT cells in peripheral blood using hSCP2 518-532 , the human counterpart of rSCP2 518-532, together with a CD1d tetramer in flow cytometry. First, we determined the binding of hSCP2 518-532 to CD1d. Next, we detected CD3-positive hSCP2 518-532 -loaded CD1d (hSCP2 518-532 /CD1d) tetramer-binding cells in peripheral blood of healthy donors. The abundance of TGF-β-producing cells rather than TNF-α-producing cells in CD3-positive hSCP2 518-532 /CD1d tetramer-binding cells suggests the anti-inflammatory property of SCP2-loaded CD1d (SCP2/CD1d) tetramer-binding type II NKT cells in healthy individuals. Furthermore, we compared cytokine profile between healthy individuals and patients with vasculitis in a pilot study. Interestingly, the percentage of TGF-β-producing cells in SCP2/CD1d tetramerbinding type II NKT cells in vasculitic patients was significantly lower than that in healthy controls despite the greater number of these cells. Although further studies to clarify the mechanism and significance of this phenomenon are needed, SCP2/CD1d tetramer-binding type II NKT cells in peripheral blood should be examined in more detail to understand the pathophysiology of vasculitides in humans.

The role of NK and NKT cells in the pathogenesis and improvement of multiple sclerosis following disease‐modifying therapies

“…Natural killer T (NKT) cells express T cell receptor and several molecular markers related to NK cells 61 . These cells detect hydrophobic antigens (lipid or glycolipid) presented by CD1d molecules similar to MHC class I 62 . The amount of NKT cells in the blood, peripheral lymph nodes, pancreatic lymph nodes, mesentery, spleen, and liver is between 0.5% and 30% of white blood cells 63 .…”

“…They express the Vα14‐Jα18 chain paired with Vβ8, Vβ7, or Vβ2 chains in rodents, or homologous Vα24‐Jα18 and Vβ11 chains in humans as the T‐cell receptor (TCR) constant chain 65‐68 . Contrary vNKT cells express more diverse TCRs than iNKT cells and display innate effector functions and can produce both Th1 and Th2 cytokines 62,64 …”

“… 61 These cells detect hydrophobic antigens (lipid or glycolipid) presented by CD1d molecules similar to MHC class I. 62 The amount of NKT cells in the blood, peripheral lymph nodes, pancreatic lymph nodes, mesentery, spleen, and liver is between 0.5% and 30% of white blood cells. 63 Natural killer T cells based on the heterogeneity of TCR rearrangement, are divided into two categories of NKT type 1 cells or classical NKT cells or invariant NKT cells (iNKT) and NKT type 2 cells or non‐classical NKT cells or diverse NKT cells (vNKT).…”

“… 65 , 66 , 67 , 68 Contrary vNKT cells express more diverse TCRs than iNKT cells and display innate effector functions and can produce both Th1 and Th2 cytokines. 62 , 64 …”

Infections, Reactions of Natural Killer T Cells and Natural Killer Cells, and Kidney Injury

“…Some researchers have proposed that human T cells expressing TCRs encoded by the Vα24Jα18 and Vβ11 genes, in which the arrangement of TCRs resembles that of mouse invariant NKT cells, are human NKT cells [ 18 ]. Indeed, these cells are activated by a specific sphingoglycolipid ligand of mouse invariant NKT cells [ 8 ], and their involvement in the pathophysiology of human diseases, including microscopic polyangiitis, a form of vasculitis that often causes damage to kidneys, was suggested [ 19 ]; however, these cells only constitute a very rare population both in the peripheral blood and liver in humans [ 14 ]. On the other hand, CD56 + T cells are a functional counterpart of mouse NKT cells in that (i) they are abundant in the liver, (ii) they show antitumor effects after cytokine stimulation, and (iii) most liver CD56 + T cells express CD161, which is identical to the NK1.1 antigen in mice.…”