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Leucocyte Immunotherapy for Recurrent Miscarriage
Published in Howard J.A. Carp, Recurrent Pregnancy Loss, 2020
In the laboratory mouse model, mating of CBA/J female mice with allogeneic DBA/2 males generates pregnancies susceptible to a high rate of spontaneous abortion (resorption) that is partner specific. Changing either the female or male strain lowers the abortion rates to <10%. The high rate of resorption in the CBA · DBA/2 model is correctable by immunization with cells bearing paternal major histocompatibility (MHC) antigens [19]. The immunization strategy against abortion in the CBA · DBA/2 model has employed freshly isolated BALB/c cells (which have the same MHC as DBA/2). However, when the allogeneic cells were stored overnight in tissue culture medium at 4°C, the beneficial effect was abrogated, resulting in a resorption rate that was identical to that without immunization [20] (Figure 29.5). The basis for this alteration was unclear. It was hypothesized that BALB/c lymphoid cells had to express certain paternal alloantigens and a tolerance co-signaling molecule, CD200 (OX-2) to induce protection [21]. Storage of BALB/c splenocytes causes loss of surface CD200 into the supernatant. Similarly, CD200 is lost if purified human blood mononuclear cells are stored. Thus, an intact cell membrane−bound CD200 molecule is required for BALB/c splenocytes to immunize against abortions in the CBA · DBA/2 model. Fresh cells were required, and cells stored overnight, even at 4°C in serum-containing medium, lost most of their activity.
Respiratory System
Published in Pritam S. Sahota, James A. Popp, Jerry F. Hardisty, Chirukandath Gopinath, Page R. Bouchard, Toxicologic Pathology, 2018
Tom P. McKevitt, David J. Lewis
AMs in the healthy lung are reported to concentrate at alveolar septal junctions (Takaro et al. 1990) and by TEM are characterized by numerous mitochondria and secondary lysosomes. Activated macrophages have been subdivided into classically activated (M1), which have largely antiproliferative, inflammatory, and cytotoxic activity, and alternatively activated (M2), which have a generally anti-inflammatory impact and are involved in the initiation of wound healing and tissue remodeling (Laskin et al. 2011). The activation state is a dynamic process; an individual macrophage may switch between states depending on its environment (Murray and Wynn 2011), and the precise profile of the AM will depend also on how it became activated (Bowdridge and Gause 2010; Mosser and Edwards 2008). The regulation of AMs by direct interaction with the airway epithelium is also an area of increasing interest. For instance, CD200, expressed on the luminal aspect of respiratory epithelium, interacts with CD200R on AMs to dampen AM proinflammatory responses (Hussell and Bell 2014). Conversely, an absence of CD200 considerably delayed resolution of lung inflammation in mice (Snelgrove et al. 2008). Markers of an activated state include inducible nitric oxide synthase for M1 macrophages and arginase 1, Fizz1, and Ym1/2 for M2 macrophages (Misson et al. 2004). CD68 IHC is commonly used as a general marker for AM; however, antibodies to this target also bind monocytes and granulocytes in the peripheral blood (Noorman et al. 1997).
Development, structure, and function of the nail
Published in Eckart Haneke, Histopathology of the NailOnychopathology, 2017
CD200 is an immunoprotective membranous molecule rendering an immune privilege to the follicular bulge.78 Given the overall weak staining for CD8 clone C8/144B and for CD200 in the fetal hair follicle and the lack of staining in the developing nail unit, it is probable that the immunosurveillance during embryogenesis has not yet attained a postnatal level.
23ME-00610, a genetically informed, first-in-class antibody targeting CD200R1 to enhance antitumor T cell function
Published in OncoImmunology, 2023
Jill Fenaux, Xin Fang, Yao-ming Huang, Cristina Melero, Caroline Bonnans, Earth Light Lowe, Tiziana Palumbo, Cecilia Lay, Zuoan Yi, Aileen Zhou, Mauro Poggio, Wei-Jen Chung, Sophia R. Majeed, Dylan Glatt, Alice Chen, Maike Schmidt, Clarissa C. Lee
Humans express a single functional CD200R1 inhibitory gene, whereas mice express multiple CD200 family receptors that act as both stimulatory and inhibitory molecules2. Differences in the pathway between mice and humans may confound interpretation of data relative to human systems, especially when considering agents that modulate CD200R1 activity. Despite these limitations, modeling of the complex TME is best recapitulated in syngeneic mouse models, so we investigated the blockade of CD200:CD200R1 signaling in mice bearing murine S91 melanoma tumors that endogenously express CD200. OX90, a CD200 blocking antibody clone that has been frequently used in published studies, was originally isolated in a rat IgG2a backbone25. Rat IgG2a can bind weakly to mouse FcγRIII and may mediate depletion of CD200 positive cells26. This could result in confounding effects as CD200 is broadly expressed, including on S91 tumor cells, B cells, and activated T cells. To avoid this, we used an Fc-silent version of OX90 for our studies, which should limit pharmacological effects to blocking CD200:CD200R1 signaling. We observed that blocking CD200:CD200R1 signaling was sufficient to promote significant tumor growth inhibition and activate expression of genes involved in immune activation, such as the IFNγ and TNFα pathways, which have been shown to be critical for CTL-mediated killing of cancer cells27,28.
CD200AR-L: mechanism of action and preclinical and clinical insights for treating high-grade brain tumors
Published in Expert Opinion on Investigational Drugs, 2022
Christopher Moertel, Francisco Martinez-Puerta, Grace G. Elizabeth Pluhar, Maria Graciela Castro, Michael Olin
The CD200 protein is secreted from human glioblastoma (manuscript in preparation), inducing systemic and tumor microenvironment immunosuppression. In addition, we discovered that CD200 is upregulated in tumor-associated vascular endothelial cells in glioblastoma, forming an ‘immunologic blood–brain barrier’ [11]. We suggest that the CD200 protein is a mechanism for the tumor to evade the immune system. In recent experiments, we discovered that knocking out the CD200 protein from the tumor cells allowed immune competent mice to spontaneously reject 100% of tumors (unpublished data). This response is immune mediated, since none of the CD200KO tumors were affected in immune incompetent mice. Therefore, we hypothesize that targeting the CD200 immune checkpoint will significantly enhance immunotherapy.
Cutaneous leishmaniasis: multiomics approaches to unravel the role of immune cells checkpoints
Published in Expert Review of Proteomics, 2022
Yasaman Taslimi, Nasrin Masoudzadeh, Fariborz Bahrami, Sima Rafati
CD200 (OX-2 membrane glycoprotein) ligand is also an immunoglobulin superfamily which is expressed on lymphoid cells, DC, endothelium and thymocytes. CD200 binds and activates the CD200 receptor (CD200R) which is widely expressed in myeloid cells such as DC, neutrophils, monocytes, and mast cells. Evidence suggests that the interaction between CD200 and CD200R can inhibit myeloid cell activation which has a consequent effect on the suppression of the immune response [72,73]. It has been demonstrated that expression of CD200 by L. amazonensis acts as a mechanism to increase the virulence potency of this parasite in the host. This action is shown to be unique and only happens if the macrophages are infected with L. amazonensis, and not with L. major [74]. The role of CD200/CD200R has also been reported in the context of L. donovani infection. Using a murine model, it has been shown that immunization with centrin-deleted L. donovani results in CD200/CD200R downregulation and activation of more specific Th1 cells [51].