Defining a novel subset of CD1d‐dependent type II natural killer T cells using natural killer cell‐associated markers

Abstract

Natural killer T (NKT) cells are αβ T cell receptor (TCR) expressing innate‐like T cells that display natural killer (NK) cell markers. Based on TCR characteristics, they are divided into two groups restricted to the MHC class I‐like molecule CD1d. Type I NKT cells, most extensively studied, are identified by a semi‐invariant Vα14‐Jα18 (mouse, Vα24‐Jα18 in humans) TCR reactive to the prototypic ligand α‐galactosylceramide presented on CD1d. In contrast, type II NKT cells display diverse TCR reacting to different CD1d‐presented ligands. There are no reagents that identify all type II NKT cells, limiting their exploration. Here, we searched for novel type II NKT cells by comparing Jα18−/−MHCII−/− mice that harbour type II but not type I NKT cells, and CD1d−/−MHCII−/− mice, lacking all NKT cells. We identified significantly larger populations of CD4+ and CD4−CD8− (double negative, DN) TCRβ+ cells expressing NKG2D or NKG2A/C/E in Jα18−/−MHCII−/− mice compared with CD1d−/−MHCII−/− mice, suggesting that 30%‐50% of these cells were type II NKT cells. They expressed CD122, NK1.1, CXCR3 and intermediate/low levels of CD45RB. Further, the CD4+ subset was CD69+, while the DN cells were CD49b+ and CD62L+. Both subsets expressed the NKT cell‐associated promyelocytic leukaemia zinc finger (PLZF) transcription factor and Tbet, while fewer cells expressed RORγt. NKG2D+ CD4+ and DN populations were producers of IFN‐γ, but rarely IL‐4 and IL‐17. Taken together, we identify a novel subset of primary CD4+ and DN type II NKT cells that expresses NKG2 receptors have typical NKT cell phenotypes and a TH1‐like cytokine production.

Altered Frequency of NK Cells and Treg Cells by Astragalus Polysaccharide Combined with Budesonide in Asthma Model Mice

“…It is documented that patients with asthma o en had increased frequencies of IL-4-producing NK cells [19].…”

Recent Development in NKT-Based Immunotherapy of Glioblastoma: From Bench to Bedside

“…For instance, NKT II cells produce IL-13 in response to tumor growth, resulting in the excretion of TGF-beta from myeloid cells that inhibits cytotoxic T cell-mediated tumor immunosurveillance in several mouse tumor models [93]. However, novel CD4 + and DN type II NKT cells that express NKG2 receptors have been demonstrated to produce the T H 1-like cytokine IFN-γ, suggesting that this novel subset of CD4 + and DN type II NKT cells are biased toward the typical NKT I cells and have Th1-like cytokines production [91]. Moreover, targeting intestinal type II NKT cells using orally delivered sulfatide facilitates intestinal immunoglobulin A (IgA), T helper 1 (Th1), and T helper 17 (Th17) responses in mice [94].…”

“…[60][61][62] Sulphatide[67] β-GlcCer, PG, PG, LPC, LPE[68][69][70][71][72][73][74][75][76][77] MICA/B NK associated receptors Mice NK1.1 (human CD161 + ) (resting mature) Mice NK1.1 (human CD161 − )/low (immature or post-activation)[60,78] Mice NK1.1 (human CD161 +/− )[60] Mice NK1.1 (human CD161 + ) Activation receptors (NKG2C, NKG2D, NKp30, NKp44, NKp46) Inhibitory receptors (CD158a, CD158b, KIR3DL1, and NKG2A)[79,80] Subsets CD4 + and DN (mice) CD4 + , CD8 + and DN (humans)[60,78] CD4 + and DN (mice)[60] CD4 + , CD8 + and DN[60] Cytokines TH1-like IFN-γ, TNF-α[81] TH2-like IL-4, IL-13 [82] TH17-like IL-17, IL-21, IL-22[83,84] Treg-like IL-10 [85-87] TFH-like-IL-21[88][89][90] TH1-like IFN-γ, TNF-α[91] TH2-like IL-4, IL-13[92,93] TH17-like IL-17, IL-21, IL-22 (mice)[94] …”

Relationship between chemokines and T lymphocytes in the context of respiratory allergies (Review)

“…response is based on the contribution of the following cells: Th2 cells (6), type 2 B cells (7), interleukin-4 (IL-4) secreting NK cells (8), IL-4 secreting T-NK cells (9), mast cells, eosinophils, basophils, their cytokines (CK) (5): IL-4, IL-5, IL-9, IL-13, along with those CKs secreted by tissue cells (5): IL-25 (10), IL-31 (11), IL-33 (12) and TSLP (13).…”

“…Historically, allergic asthma and rhinitis were hypothesized to be produced by this type of mechanism ( 4 , 5 ). Type 2 immune response is based on the contribution of the following cells: Th2 cells ( 6 ), type 2 B cells ( 7 ), interleukin-4 (IL-4) secreting NK cells ( 8 ), IL-4 secreting T-NK cells ( 9 ), mast cells, eosinophils, basophils, their cytokines (CK) ( 5 ): IL-4, IL-5, IL-9, IL-13, along with those CKs secreted by tissue cells ( 5 ): IL-25( 10 ), IL-31( 11 ), IL-33( 12 ) and TSLP ( 13 ). Starting from the characterization of Th2 endotype, experts identified two endotypes: Th2-high and Th2-low ( 14 ), which were divided further in several sub-endotypes: IL-5-high, IL-13-high, IgE-high ( 5 ).…”