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Specific Host Restance: The Effector Mechanisms
Published in Julius P. Kreier, Infection, Resistance, and Immunity, 2022
Cytolytic T lymphocytes (CTLs) are lymphocytes programmed to destroy target cells in an antigen-specific fashion. They are T cells identified by the CD8 protein on their surface and are therefore referred to as CD8+. They have been extensively studied because they are the cells primarily responsible for graft rejection (chapter 11). CTLs are also capable of recognizing virus and other parasite-produced proteins present on the surfaces of host cells in association with Class 1 MHC molecules (Figure 9.11). Despite the damage to the host which may result from the destruction of infected host cells, the recognition and destruction of viruses and other intracellular parasites by the destruction of infected host cells is the only way the host can rid itself of such infections.
Biomarkers for the Immune Checkpoint Inhibitors
Published in Sherry X. Yang, Janet E. Dancey, Handbook of Therapeutic Biomarkers in Cancer, 2021
Weijie Ma, Sixi Wei, Eddie C. Tian, Tianhong Li
A major goal of active immunotherapy against cancer is the activation of antigen-specific and tumor-reactive CD8+ T-cells. Inhibition of CTLA-4 or PD-1/PD-L1 leads to a broadening of the T cell receptor (TCR) repertoire in melanoma patients [69, 70]. TCR sequencing has offered information on T cell clonal diversity, which has been found to correlate with H&E lymphocyte scoring [71]. Assessment of peripheral T-cell population characteristics—particularly the T-cell receptor gene sequences or reactivity to neoantigens—could potentially play a role as predictive biomarkers. Current technology is mainly based on a multiplex PCR-based method which can define the number and frequency of immunoglobulin heavy chains or T-cell receptor (TCR) a, ß, y chains expressed in lymphocytes. RNA sequencing can assess the TCR repertoire diversity comprehensively compared to that of droplet digital Polymerase Chain Reaction (ddPCR) [72]. Furthermore, single cell RNA sequencing is a powerful tool to obtain a comprehensive profiling of the transcriptome of individual human T and B cells [73–75]. Analyses of the genes responsible for T cell activation, apoptosis, cellular proliferation, cytotoxic response, and T cell differentiation towards effector versus regulator could further show the specific points of intervention for active specific blockage of Treg cells.
Interleukin 12: A Potent Vaccine Adjuvant for Promoting Cellular Immunity and Modulating Humoral Immunity
Published in Thomas F. Kresina, Immune Modulating Agents, 2020
In studies perhaps more directly relevant to clinical practice, several investigators have demonstrated the efficacy of IL-12 as an adjuvant in therapeutic antitumor vaccination. The Meth A sarcoma is heterozygous for three missense point mutations in the tumor suppressor gene p53. The peptide encoding one of these is capable of eliciting peptide-specific CD4+ and CD8+ T cell responses [12]. Vaccination with this peptide in combination with QS21 given subcutaneously and IL-12 given i.p. elicited a T cell response and cured mice of established tumor [13]. Immunization with any combination other than all three was not effective. The importance of both CD4+ and CD8+ cells was demonstrated by depletion with antibodies. Depletion of CD4+ cells at the primary but not the boost immunization abrogated the response. Depletion of CD8+ cells at either the primary immunization or the boost abrogated the therapeutic response.
Adipose-Derived Mesenchymal Stem Cells Attenuate Immune Reactions Against Pig Decellularized Bronchi Engrafted into Rat Tracheal Defects
Published in Organogenesis, 2023
Makoto Hisanaga, Tomoshi Tsuchiya, Hironosuke Watanabe, Koichiro Shimoyama, Mayumi Iwatake, Yukinori Tanoue, Keizaburo Maruyama, Hiroshi Yukawa, Kazuhide Sato, Yoshimi Kato, Keitaro Matsumoto, Takuro Miyazaki, Ryoichiro Doi, Koichi Tomoshige, Takeshi Nagayasu
Infiltrating macrophages have either a proinflammatory (M1) or anti-inflammatory (M2) phenotype.35,36 Immunochemistry results for CD8 (a cytotoxic T lymphocyte marker), CD68 (a pan-macrophage marker), and CD163 (an M2 macrophage marker) in the tissue surrounding the implanted engineered trachea are shown in Figure 4a. We used CD8 expression as a marker for T-cells. The number of CD8+ lymphocytes was significantly lower in the Decellularized Xenograft+ADMSC group relative to the native and Decellularized Xenograft groups (Figure 4b; p = 0.049 and p = 0.0062, respectively). The number of CD68+ macrophages was similar in all groups. However, comparison with results in the Decellularized Xenograft group revealed that ADMSC administration significantly increased CD163+ cell infiltration into the tissues surrounding the grafts (Figure 4b; p = 0.0026). The number of CD163+ cells in the Decellularized Xenograft+ADMSC group was thus significantly higher than that in the native group (Figure 4b; p = 0.0016).
A diversity outbred F1 mouse model identifies host-intrinsic genetic regulators of response to immune checkpoint inhibitors
Published in OncoImmunology, 2022
Justin B. Hackett, James E. Glassbrook, Maria C. Muñiz, Madeline Bross, Abigail Fielder, Gregory Dyson, Nasrin Movahhedin, Jennifer McCasland, Claire McCarthy-Leo, Heather M. Gibson
CD8 infiltration was determined via Immunohistochemistry. Briefly, Formalin Fixed Paraffin Embedded sections were deparaffinized and rehydrated in Xylene and Ethanol rinses prior to antigen decloaking via heat pressure for 10 sec 105°C and 10 sec 95°C. Normal horse serum was used for nonspecific blocking and Rabbit anti-mouse CD8α (clone D4W27, Cell Signaling Technology®) was used as detection antibody. ImmPRESS® Horse Anti-Rabbit IgG Polymer Kit (Vector Laboratories) was used for secondary antibody and chromagen reaction using the ImmPACT® Vector® Red kit (Vector Laboratories). Tissues were counterstained with Mayer’s Hematoxylin (Thermo scientific) and then dehydrated in Ethanol and Xylene rinses before being mounted with Permount® (Fisher). To determine CD8 infiltration in tumor sample after staining slides were scanned with a SCN 400-Slide Scanner (Leica). Representative scan images were used to train a Weka Segmentation69 classifier on tumor, melanin, and positive staining. After segmentation images were converted to 8 bit and positive staining was set to red using image threshold. Images were then converted to black and white filtering out all features other than positive staining. Positive staining regions were filled in using a fill holes function and clustered objects were split using a watershed function. Positive cells were finally counted using a minimum circularity of 0.3 and a size exclusion of 200–20,000 pixels. A representative image showing the process from slide image to counted positive cells can be seen in Fig. S6.
Cow milk exosomes activate NK cells and γδT cells in human PBMCs in vitro
Published in Immunological Medicine, 2020
Shihoko Komine-Aizawa, Shun Ito, Shu Aizawa, Takahiro Namiki, Satoshi Hayakawa
CM-Ex stimulation upregulated cell surface CD69 expression. (A) The gating strategy used to identify CD8+ T cells, CD16 + CD56dim NK cells and CD16−CD56bright NK cells in PBMCs is shown. The upper 4 panels show the initial gating of the total events, including a singlet gate, followed by selection for lymphocytes among live CD3+ T cells or CD3− cells. CD8+ and CD4+ T cells were further identified by CD8 and CD4 expression, respectively. CD16+CD56dim NK cells and CD16−CD56bright NK cells were further identified by CD16 and CD56 expression, respectively. (B) Representative pseudocolour plot of CD69 and NKG2D expression in CD8+ T cells, CD16+CD56dim NK cells and CD16−CD56bright NK cells, with NKG2D on the x-axis and CD69 on the y-axis. The left panel represents CD69 and NKG2D expression without IL-2 + IL-12, and the right panel represents CD69 and NKG2D expression with IL-2 + IL-12. (C) The expression of CD69 and NKG2D in CD8+ T cells, CD16+CD56dim NK cells and CD16−CD56bright NK cells after 5 h of stimulation by CM-Exs with or without IL-2 + IL-12. **p < 0.01; *p < 0.05. Tukey–Kramer test. Sample size was n = 5 for normal healthy volunteers.