Intraepithelial T cells: Specialized T cells at epithelial surfaces
Phillip D. Smith, Richard S. Blumberg, Thomas T. MacDonald in Principles of Mucosal Immunology, 2020
Despite this, intestinal IETs share unique phenotypic and functional characteristics that distinguish them from systemic T cells in the periphery. First, there are more T cells residing within the gut epithelium than there are in other tissues. B cells are rare and only present in specialized epithelium overlying Peyer's patches (PP). Second, IETs include an abundance of γδ T-cell receptor (TCR) expressing cells. Third, IETs are antigen-experienced cells; however, they do not express markers of recently activated cells, such as CD25. Fourth, the majority of IETs display a typical cytotoxic phenotype, but at steady state they secrete only low levels of effector cytokines. Fifth, and typical of stress-sensing cells, IETs also express innate activating and inhibitory natural killer (NK) cell-like receptors. Sixth, IETs express the αEβ7 integrin (CD103 indicates the αE chain), which interacts with E-cadherin on the epithelial cells. Seventh, IETs express activation markers such as CD69 and CD8αα homodimers, a hallmark of activated cells. (The ligand for CD8αα, the nonclassical major histocompatibility complex [MHC] class I molecule thymus leukemia antigen, is also abundantly and constitutively expressed on gut epithelial cells.) Eighth, a large fraction of TCRαβ IETs are CD4−CD8− double negative, typical of high-affinity T cells. They express a limited repertoire of TCR-α and TCR-β chains and are thus considered to be oligoclonal. Finally, IETs display a typical “restrained” phenotype hallmarked by the expression of molecules like CD160, CD244, CRTAM, and LAG3.
Immunological causes of recurrent implantation failure
Efstratios M. Kolibianakis, Christos A. Venetis in Recurrent Implantation Failure, 2019
Prednisolone, which belongs to glucocorticoids, is the most widely prescribed treatment for immunomodulation in patients with infertility and RIF due to its easy application, low cost, and relative safety in short-term treatment regimes. Prednisolone was reported to be effective in RIF women with high NK cell levels and/or activity.20,40 In a randomized controlled, prospective study, prednisolone 20 mg was given to women undergoing ICSI treatment. Patients with elevated NK cell activation marker (CD69+ >1% of total lymphocytes) by flow cytometric analysis were included. Women with an immunological disease, thrombophilia, or uterine or endometrial abnormalities were excluded. Clinical pregnancy rate of women with prednisolone (n = 58) was 48.3% as compared with 29.6% in controls (n = 54, p < 0.05, RR 1.63, CI 1.00–2.66).20 Prednisolone induces maternal immune tolerance by decreasing peripheral blood NK cell levels and activities. It has been hypothesized that elevated peripheral blood CD56bright NK cells in the failed IVF cycle may account for reduced decidual recruitment and predict implantation failure.41 One week after ET, women with failed IVF showed elevated peripheral blood NK (both CD56bright and CD56dim) and NKT-like cell proportions, increased perforin-containing CD56bright cells, more activated and degranulated CD56dim NK cells, and enhanced NK cell-activating receptor expression on both cell types and both NK cell subsets (CD160, NKG2D).42 All these findings reflect unfavorable type 1 changes of NK and NKT-like cells during this period.
Combining phage display with SMRTbell next-generation sequencing for the rapid discovery of functional scFv fragments
Published in mAbs, 2021
Francesco Nannini, Lenart Senicar, Farhaan Parekh, Khai J. Kong, Alexander Kinna, Reyisa Bughda, James Sillibourne, Xihao Hu, Biao Ma, Yuchen Bai, Mathieu Ferrari, Martin A. Pule, Shimobi C. Onuoha
We sought to determine the quality and diversity of CD160-binding antibodies obtained through NGS analysis. We devised a simple workflow for the identification and testing of scFv antibodies (Figure 3). Initially, to identify binders, we based our analysis on the frequency of heavy chains and further searched for unrelated clones based on unique IGHV usage. The strategy was applied to data from pan 3 of the CD160 library. Here, we sorted for antibody clonotypes, defined as clones with identical HCDR3 sequence. Within each clonotype family several variants existed with substitutions in HCDRs 1 and 2. A single clone within each clonotype family was selected, based on the distance of HCDRs 1 and 2 from germline, for further characterization. In previous experiments we identified 5 clonotypes through conventional phage display selection and screening of over 200 phage clones.20 All clonotypes found through conventional screening methods were observed in the NGS data set.
TIGIT+ TIM-3+ NK cells are correlated with NK cell exhaustion and disease progression in patients with hepatitis B virus‑related hepatocellular carcinoma
Published in OncoImmunology, 2021
Lihua Yu, Xiaoli Liu, Xinhui Wang, Fengna Yan, Peng Wang, Yuyong Jiang, Juan Du, Zhiyun Yang
To characterize the phenotype of NK cells that co-expressed TIGIT+TIM-3+ in HBV-HCC patients, we detected the expression of several inhibitory receptors on TIGIT+TIM-3+ NK cells. We found that the expression level of CD39 was significantly higher in the TIGIT+TIM-3+ NK cells than the TIGIT−TIM-3− NK cells in HBV-HCC patients (P < .0001, Figure 6a). The expression level of LAG-3 and BTLA was significantly higher in the TIGIT+TIM-3+ NK cells than TIGIT−TIM-3− and TIGIT+TIM-3− NK cells in HBV-HCC patients (P < .001, Figure 6b, c). Besides, the expression level of CD160 on TIGIT+TIM-3+ NK cells increased significantly, compared with TIGIT−TIM-3−, TIGIT+TIM-3−and TIGIT−TIM-3+NK cells (P < .05, Figure 6d). TIGIT+TIM-3+ NK cells highly expressed co-inhibitory molecules, such as CD160, so they exhibited an exhausted phenotype.
Concurrent gut transcriptome and microbiota profiling following chronic ethanol consumption in nonhuman primates
Published in Gut Microbes, 2018
Tasha Barr, Suhas Sureshchandra, Paul Ruegger, Jingfei Zhang, Wenxiu Ma, James Borneman, Kathleen Grant, Ilhem Messaoudi
Similarly, in the jejunum, STEM analysis revealed a cluster of genes whose expression increases with non-heavy ethanol consumption then returns to near control levels with heavy ethanol consumption (Fig. 4B; Supplemental Table 2). Majority of these 129 genes are important for cellular metabolism, and functionally enriched to the GO term “cellular metabolic process” (n = 80; FDR-P = 5.16e-3) including the Acetyl-CoA Acetyltransferase 1 ACAT1 and the ubiquitin ligase MARCH7. STEM also identified a second group of genes with expression that increases with non-heavy ethanol consumption and remains unchanged with heavy ethanol consumption (Fig. 4B; Supplemental Table 2) that also functionally enriched to GO term “metabolic process” (FDR-P = 8.42e-2; Fig. S1B) including the phosphofructokinase PFKM and the solute carrier SLC7A7. STEM further identified a third cluster of genes in the jejunum, with expression levels that drastically increase with non-heavy ethanol consumption then continue to increase with heavy ethanol consumption (Fig. 4B; Supplemental Table 2). These genes are critical for signal transduction and include natural killer cell receptor CD160 and the choline phosphotransferase CEPT1.
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