Search

Th2 cells are well known to play important roles in allergic diseases including allergic rhinitis (AR). Meanwhile, the factors that induce and sustain the pathogenesis of AR remain unclear. The recent development of sublingual immunotherapy (SLIT) is expected to allow changes to the underlying pathogenesis of AR. However, the phenotype of the pathogenic Th2 cells (Tpath2) cells in house dust mite-induced AR (HDM-AR) and the relation between Tpath2 and SLIT efficacy have not been clarified. Therefore we analyzed the cytokine production and frequency of HDM-reactive T-cell subsets in peripheral blood mononuclear cells (PBMCs) using flow cytometry in 89 HDM-AR patients (placebo; n = 43 and HDM 300 IR; n = 46) who participated in a placebo-controlled study of SLIT with HDM tablets. All patients provided samples both before treatment as a baseline and at the end of the 52-week study. HDM-reactive IL-5 + IL-13 + CD27 - CD161 + CD4 + cells and ST2 + CD45RO + CD4 + cells were observed in the PBMCs from each patient with HDM-AR; these cells significantly decreased after SLIT in the group treated with active tablets. HDM-reactive ST2 + CD45RO + CD4 + cells were significantly lower in active-responders. In conclusion, HDM-reactive ST2 + CD45RO + CD4 + cells or those combined with IL-5 + IL-13 + CD27 - CD161 + CD4 + cells may be useful as markers indicating the successful treatment of SLIT. These cells may play a crucial role in the pathogenesis of HDM-AR as Tpath2.

CD1d-restricted invariant natural killer T (iNKI) cells are the unique lymphocyte subpopu- lation that interacts with glycolipid via the invariant T cell receptor. Ligand activated iNKT cells produce a variety of cytokines, and thus bridging the innate and adaptive immune sys- tems. Since recent studies have highlighted iNKT cells to have potent anti-tumor effects, greater attention are being given to the development of iNKT cell-based immunotherapy for advanced solid tumors. This article summarizes the progress of our recent works on active immunotherapies aiming at the augmentation of iNKT cell function in vivo in patients with non-small cell lung cancer, and discusses the role of iNKT cell-induced immune responses in cancer immunotherapy.

Myeloid-derived suppressor cells (MDSC) are a heterogeneous population of immature and progenitor myeloid cells with an immunosuppressive role in various types of cancer, including head and neck squamous cell carcinoma (HNSCC). However, the effect on the host immune system, especially on invariant NKT (iNKT) cells with potent anti-tumor activity, remains unclear. In this study, we investigated the effects of circulating MDSC subsets on the peripheral lymphocytes of patients with head and neck tumors. A significant accumulation of CD15+ granulocytic MDSC (G-MDSC) and CD14+ monocytic MDSC (M-MDSC) was demonstrated in HNSCC patients. The percentage of G-MDSC showed an inverse correlation with the percentage of T cells in the peripheral blood. The increased G-MDSC was significantly associated with advanced clinical stage and poor prognosis of HNSCC patients. The proliferation and viability of T cells were suppressed by CD15+ cells, and the suppression was reversed by adding the hydrogen peroxide scavenger catalase. However, iNKT cell activation upon α-galactosylceramide (αGalCer) stimulation was not affected by the presence or absence of CD15+ G-MDSC. These results indicate that increased G-MDSC negatively affects peripheral T cell immunity, but not iNKT cells, in HNSCC patients, and that T cells are more sensitive to hydrogen peroxide produced by G-MDSC than iNKT cells. Cancer immunotherapy designed to enhance the antitumor activity of iNKT cells by stimulation with αGalCer may remain effective in the presence of G-MDSC., (© 2015 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.)

The microvascular architecture of the human cerebral subcortical white matter was studied. Most of the subcortical arteries ran straight through the cortex, but upon entering the white matter, they began to coil, loop, and spiral. Vascular stains showed wide spaces between the adventitial sheaths and blood vessels. The blood vessels coiled, looped, and spiraled within these wide adventitial spaces. This phenomenon was observed in the brains from persons ranging from the first to ninth decades of life and there were no statistically significant age-related correlations. Furthermore, there was no evidence of a reduction in the volume of white matter after fixation. Therefore, the observed tortuosity does not appear to be the result of shrinkage of brain tissue following fixation. While the mechanisms responsible for the subcortical arteries circuitry remain undetermined, this coiling architecture may serve as a trap for tumor cells and microorganisms passing through the blood stream, suggesting that these coiling arterial blood vessels may play a significant role in the pathogenesis of tumor metastasis and the brain abscess that frequently occurs in the gray-white matter junction.