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Intraepithelial T cells: Specialized T cells at epithelial surfaces
Published in Phillip D. Smith, Richard S. Blumberg, Thomas T. MacDonald, 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
Published in Efstratios M. Kolibianakis, Christos A. Venetis, Recurrent Implantation Failure, 2019
Ari Kim, Wael Saab, Nayoung Sung, Joanne Kwak-Kim
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.
Blockade of programmed cell death protein 1 (PD-1) in Sézary syndrome reduces Th2 phenotype of non-tumoral T lymphocytes but may enhance tumor proliferation
Published in OncoImmunology, 2020
Ieva Saulite, Desislava Ignatova, Yun-Tsan Chang, Christina Fassnacht, Florentia Dimitriou, Eleni Varypataki, Florian Anzengruber, Mirjam Nägeli, Antonio Cozzio, Reinhard Dummer, Julia Scarisbrick, Steve Pascolo, Wolfram Hoetzenecker, Malgorzata Bobrowicz, Emmanuella Guenova
The glycoprotein cutaneous lymphocyte-associated antigen (CLA) is expressed on the cell surface of tumor lymphocytes and can be used for the identification of skin-homing T cells.46 Skin‐resident CD4+ T cells express NK receptors, CD160 and CD158 k (KIR3DL2) being amongst the most stably observed and relative ones for CTCL.47 In our study cohort, CLA was expressed on 71.36% of all lymphocytes in L-CTCL patients and on 42.6% of all lymphocytes in healthy individuals (p = .00000068, Figure 3(a)). Within the subset of TCR Vβ clonal tumor cells, 77.26% of the cells expressed CLA. In particular, PD-1 expressing tumor T cells were preferentially CLA positive and thus skin tropic (p = .03; Figure 3(b)). Further, tumor cells showed a tendency for enhanced CD160 expression (Suppl. Figure 1a), especially within the fraction of skin-homing (Suppl. Figure 1b) or PD-1+ (Suppl. Figure 1c) T cells. CD158 k is known to be often expressed on malignant T-cells.48,49 In the limited number of patients, from which samples were available for this analysis, expression of CD158 k did not significantly differ depending on clonality (Suppl. Figure 1d) or skin-homing capacity (Suppl. Figure 1e) of the T cells but was strikingly and almost exclusively restricted to PD-1+ T cells only (Suppl. Figure 1f).