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Immunodeficiency Diseases
Published in Pudupakkam K Vedanthan, Harold S Nelson, Shripad N Agashe, PA Mahesh, Rohit Katial, Textbook of Allergy for the Clinician, 2021
Flow cytometry for CD3, CD4. CD8, CD 45RO and CD 45RA T cells, CD 19 or 20, CD 27 and CD 16/56/57. Additional markers that are useful include CD 40L (CD154 0n activated T cells), IL-2 receptor γ chain (CD132), MHC class I and class II, IL-7 receptor α chain (CD127), CD3 λ and δ chains and WASP
Pathogenesis of Tuberculosis
Published in Lloyd N. Friedman, Martin Dedicoat, Peter D. O. Davies, Clinical Tuberculosis, 2020
Divya B. Reddy, Jerrold J. Ellner
Maintaining an efficacious anti-TB Th1 T effector (Teff) response is dependent on counter-regulation by an additional subset of CD4+ T cells, termed natural regulatory T cells (Tregs). Treg cells are commonly identified by constitutive expression of CD25 (IL-2 receptor), FoxP3 (transcription factor), and reduced expression of CD127 (IL-7 receptor) and are responsible for suppressing Teff cell proliferation and cytokine expression.226 The main suppressive mediators expressed by Tregs are IL-10 and TGF-β. Tregs are recognized as important in regulating inflammation. Treg have been reported to be increased in number and suppressive of MTB-stimulated production of IFN-γ227 but this has not been a consistent finding. Blocking studies that a subpopulation expanded in TB, HLA-DR+ Teff are compromised to Treg-mediated suppression mediated through the β-chemokine receptor CCR5 as well as through the negative regulatory molecule, PD-L1.249 Both CCR5 and PD-L1 are reported to promote Treg suppression. HLA-DR+ Teff express higher levels of Th1/Th17 cytokines (IFN-γ, IL-17, and IL-22) that negatively regulate Tregs.
Overview of the mucosal immune system structure
Published in Phillip D. Smith, Richard S. Blumberg, Thomas T. MacDonald, Principles of Mucosal Immunology, 2020
Reinhard Pabst, Per Brandtzaeg
Whether the same sequence of events occurs in humans is difficult to determine. An LTi cell, which is CD127+, RORC+ and CD4−, has been described in fetal human tissues. The lack of CD4 on the human LTi cell is somewhat surprising because many years ago human fetal gut was shown to contain clusters of CD4+ CD3− cells, which were presumed to be the earliest PP anlagen. However, immunostaining for VCAM-1 is extremely strong in putative PPs beginning at 11 weeks of gestation, suggesting that even in man, VCAM-1 is involved in mucosal lymphoid tissue organogenesis. Beginning at 14–15 weeks of gestation, human small intestine contains loose accumulations of T cells and B cells and strongly major histocompatibility complex (MHC) class II+ cells, but the mucosa lacks follicular structure. By 19 weeks, organized small PPs with a FAE, primary B-cell follicles, and T-cell zones can be seen. A population of CD11c+ DCs clusters below the FAE, as shown in adult PPs. Although little information on the development between 20 weeks and birth is available, analysis of available specimens shows large well-organized Peyer's patches in 1- to 2-day-old tissues, containing what appear to be early secondary follicles with IgM+ blasts in the developing germinal centers, presumably in response to intestinal colonization with microbes.
Vaccine-induced CD8 T cells are redirected with peptide-MHC class I-IgG antibody fusion proteins to eliminate tumor cells in vivo
Published in mAbs, 2020
Cornelia Fischer, Michael W. Munks, Ann B. Hill, Richard A. Kroczek, Stefan Bissinger, Verena Brand, Martina Schmittnaegel, Sabine Imhof-Jung, Eike Hoffmann, Frank Herting, Christian Klein, Hendrik Knoetgen
CD8 T cells from the blood and tumor were analyzed by flow cytometry after the second treatment (Figure 8). In non-vaccinated vehicle-treated mice, the phenotype of CD8 T cells could only be characterized in the blood, due to insufficient CD8 T cell numbers in the tumor. Vaccination alone increased the number of T cells in the tumor. All CD8 T cells in the tumor expressed the trafficking molecule CD44. Upon treatment with M38-αFAP or TCB-αFAP, but not with control IE3-αFAP, both M38-specific and bystander CD8 T cells expressed upregulated levels of CD44 in the tumor but not in the blood. For the non-M38-specific CD8 T cells, CD44 was not expressed. CD62L was absent in tumor and expressed only on nonspecific CD8 T cells in blood. CD127 was slightly higher on CD8 T cells in tumor in treated groups. In blood, CD127 was reduced by treatment. Expression of surface markers in M38-specific CD8 T cells generated by vaccination was characterized as effector memory T cells (CD44+, CD62L-, and CD127+) both in the tumor and in the blood (Figure 8a). The non-M38-specific CD8 T cells were effector memory T cells (CD44+ CD62L-CD127+) in the tumor and either memory or naïve T cells (CD44+ or CD44- and CD62L+CD127+) or T cells in the transition phase in the blood.
The TLR9 agonist (GNKG168) induces a unique immune activation pattern in vivo in children with minimal residual disease positive acute leukemia: Results of the TACL T2009-008 phase I study
Published in Pediatric Hematology and Oncology, 2019
Rebecca Ronsley, Amina Kariminia, Bernard Ng, Sara Mostafavi, Gregor Reid, Peter Subrt, Nobuko Hijiya, Kirk R. Schultz
Interleukin 7 R (IL7R) gene results in transcription of IL-7 protein receptor alpha chain, CD127. IL-7 receptor is found in both B and T lymphocytes and appears to be important in regulation of the inflammatory response.39 IL7R appear to be important in T cell homeostasis in acute GvHD after hematopoietic stem cell transplant, a response important in development of the graft-versus-leukemia response.40 In acute GvHD, the IL-7/sIL-7Rα ratio was significantly higher in patients developing grades II-IV acute GvHD. Moreover, CD8+ T cell engraftment after lymphodepletion such as in HSCT, is IL7Rα dependent.41 Inhibition of IL7R may also act as a checkpoint inhibitor if CD127 (IL7R) expression CD56bright NK regulatory cell populations,42 a population important in suppressing GvHD and viral responses.43
Effects of tacrolimus (FK506) and mycophenolate mofetil (MMF) on regulatory T cells and co-inhibitory receptors in the peripheral blood of human liver allograft patients
Published in Immunopharmacology and Immunotoxicology, 2019
Qiang Zeng, Xiao-Ye Yuan, Wei Li, Bao-Wang Liu, Xin Zhao, Gui-Jun Ren, Yang Wang, Jian Dou, Gui-Ying Wang
Liver transplantation is the most effective method to treat end stage liver disease. At present, how to induce the immunological tolerance and to inhibit the chronic graft rejection represents an important trend in the field of transplantation. Tregs are a group of T cell subsets with immunosuppressive actions and play important roles in regulating immune status, inhibiting tumor immunity and inducing immune tolerance. At present, Tregs are considered to be one of the key players in clinical immune tolerance [16].CD4+CD25+Treg cells play immunosuppressive effects after organ transplantation [17]. CD4+CD25+Foxp3+ cells were used to define Tregs formerly, but recent study showed that low expression of CD4+CD25+CD127low/- cells can replace CD4+CD25+Foxp3+ cells as surface markers of Tregs. CD127 is the α-chain of the IL-7 receptor, which is expressed on the majority of mature T cells and plays an important role in their proliferation. CD127 is negatively correlated with Foxp3 expression [18], and CD4+T cells highly expressed CD127 after activation. Regulatory T cells are really activated only lowly expressed CD127 [19], and these markers did not require destruction of the cell membrane. Therefore, CD4+CD25+CD127low/-Treg cells are considered to be the best cell marker for Tregs, and are used to define Tregs in this study.