Immunologic Monitoring of Transplant Rejection: Correlation of in vitro Assays with Morphologic Changes on Transplant Biopsy

Nephron ◽  
1978 ◽  
Vol 22 (1-3) ◽  
pp. 208-211 ◽  
Author(s):  
M.R. Garovoy ◽  
P. Gailiunas ◽  
C.B. Carpenter ◽  
G.J. Busch
Keyword(s):  
Transplant Rejection ◽  
Immunologic Monitoring ◽  
Transplant Biopsy ◽  
Morphologic Changes

scholarly journals MiR-146a regulates regulatory T cells to suppress heart transplant rejection in mice

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Jian Lu ◽  
Weiwei Wang ◽  
Peiyuan Li ◽  
Xiaodong Wang ◽  
Chao Gao ◽  
...  
Keyword(s):  
T Cells ◽  
Regulatory T Cells ◽  
Heart Transplant ◽  
Transplant Rejection ◽  
Mouse Heart ◽  
Allograft Survival ◽  
Treg Function ◽  
Ifn Γ ◽  
Heart Transplant Rejection

AbstractRegulatory T cells (Tregs), which characteristically express forkhead box protein 3 (Foxp3), are essential for the induction of immune tolerance. Here, we investigated microRNA-146a (miR-146a), a miRNA that is widely expressed in Tregs and closely related to their homeostasis and function, with the aim of enhancing the function of Tregs by regulating miR-146a and then suppressing transplant rejection. The effect of the absence of miR-146a on Treg function in the presence or absence of rapamycin was detected in both a mouse heart transplantation model and cell co-cultures in vitro. The absence of miR-146a exerted a mild tissue-protective effect by transiently prolonging allograft survival and reducing the infiltration of CD4+ and CD8+ T cells into the allografts. Meanwhile, the absence of miR-146a increased Treg expansion but impaired the ability of Tregs to restrict T helper cell type 1 (Th1) responses. A miR-146a deficiency combined with interferon (IFN)-γ blockade repaired the impaired Treg function, further prolonged allograft survival, and alleviated rejection. Importantly, miR-146a regulated Tregs mainly through the IFN-γ/signal transducer and activator of transcription (STAT) 1 pathway, which is implicated in Treg function to inhibit Th1 responses. Our data suggest miR-146a controls a specific aspect of Treg function, and modulation of miR-146a may enhance Treg efficacy in alleviating heart transplant rejection in mice.

scholarly journals Bone marrow graft rejection as a function of antibody-directed natural killer cells.

1985 ◽  
Vol 161 (3) ◽  
pp. 563-576 ◽  
Author(s):  
J F Warner ◽  
G Dennert
Keyword(s):  
Bone Marrow ◽  
Nk Cells ◽  
Natural Killer ◽  
Graft Rejection ◽  
Transplant Rejection ◽  
Conclusive Evidence ◽  
Antigenic Determinants ◽  
Marrow Graft

There is conclusive evidence that acute bone marrow transplant rejection in lethally irradiated mice is caused by natural killer (NK) cells. The rejection of marrow allografts is exquisitely specific and is controlled by antigenic determinants encoded in or near the H-2 gene complex. The specificity of in vivo marrow graft rejection contrasts with the in vitro specificity pattern of NK cells in cytotoxicity assays. We therefore examined how NK cells cause H-2-specific marrow graft rejection in vivo. Several experimental approaches are presented that suggest that natural antibody, present in responder strains of mice, specifically directs NK cells in an antibody-dependent cytolytic and/or cytostatic reaction, resulting in marrow graft rejection. The following evidence for this mechanism is documented. The ability to reject a marrow graft can be passively transferred by serum from responder to allogeneic nonresponder mice and the specificity of rejection can be mapped within the H-2 region. Serum-induced marrow graft rejection is abrogated following depletion of immunoglobulin, and the serum of responder mice is able to induce a specific antibody-dependent cytotoxic reaction in vitro.

303. Further characterisation of lymphocyte-suppressing activity in gonadal fluids

2005 ◽  
Vol 17 (9) ◽  
pp. 129
Author(s):  
M. Crane ◽  
L. Foulds ◽  
J. Muir ◽  
D. Aridi ◽  
P. Hutchinson ◽  
...  
Keyword(s):  
T Cell ◽  
T Cell Activation ◽  
Cell Activation ◽  
Transplant Rejection ◽  
Calf Serum ◽  
Autoimmune Response ◽  
T Cell Anergy ◽  
Activation Assay ◽  
Proliferation In Vitro

Protection of the developing gametes from an autoimmune response within the testis and ovary is essential for reproductive success, and autoimmune infertility represents a failure of this protection. The gonads also represent favorable sites for grafts of foreign tissue, that is, they are ‘immunologically privileged’. The actual mechanisms responsible for testicular and ovarian immune privilege are poorly understood. However, it has been well established that testicular interstitial fluid and ovarian fluid have profound inhibitory effects on T-cell activation and proliferation in vitro. We have established previously that a partially purified preparation of the inhibitor, isolated from bovine follicular fluid, suppresses proliferation in an in vitro T-cell activation assay, through induction of T-cell anergy and/or atypical apoptosis. Addition of increasing doses of normal fetal calf serum and/or bovine serum albumin blocks the actions of the inhibitor and progressively increases the ED50 of the assay. It has also been shown that stimulating the T-cells with phorbol-12-myristate-13-acetate (PMA) in place of a polyclonal mitogenic stimulus such as phytohaemagglutinin bypasses the anergic effects of the inhibitor. These results suggest that the activity of the inhibitor may be negatively regulated in the circulation and tissues by serum-derived proteins and other factors. These data also indicate that the inhibitor’s activity is mediated through a specific cellular pathway, most likely involving protein kinase C isotypes, which are activated by PMA. Further work will delineate the molecular pathways and mechanisms of serum regulation of the gonadal lymphocyte-suppressing activity, which may be exploited in the treatment of autoimmune diseases and for prevention of transplant rejection.

In vitro Bactericidal Activities of Antimicrobial Agents and Morphologic Changes on Prevotella bivia

Chemotherapy ◽  
1999 ◽  
Vol 45 (5) ◽  
pp. 342-348 ◽  
Author(s):  
Hiroshige Mikamo ◽  
Yasumasa Sato ◽  
Yoh Hayasaki ◽  
Kyoko Kawazoe ◽  
Koji Izumi ◽  
...  
Keyword(s):  
Antimicrobial Agents ◽  
Prevotella Bivia ◽  
Bactericidal Activities ◽  
Morphologic Changes

Morphologic changes produced by amdinocillin alone and in combination with beta-lactam antibiotics: In vitro and in vivo

1983 ◽  
Vol 75 (2) ◽  
pp. 30-41 ◽  
Author(s):  
Michael J. Kramer ◽  
Yolanda R. Mauriz ◽  
Maria D. Timmes ◽  
Tamara L. Robertson ◽  
Roy Cleeland
Keyword(s):  
Beta Lactam ◽  
Beta Lactam Antibiotics ◽  
Morphologic Changes

Angiopoietin-2 promotes inflammatory lymphangiogenesis and its effect can be blocked by the specific inhibitor L1-10

2012 ◽  
Vol 302 (1) ◽  
pp. H215-H223 ◽  
Author(s):  
Zhi-Xin Yan ◽  
Zhao-Hua Jiang ◽  
Ning-Fei Liu
Keyword(s):  
Endothelial Cells ◽  
Vascular Endothelial Cells ◽  
Transplant Rejection ◽  
Lymphatic Vessels ◽  
Specific Inhibitor ◽  
Biological Behavior ◽  
Tnf Α ◽  
Inflammatory Stimuli ◽  
Angiopoietin 2

Angiopoietin (Ang)-2, a ligand of the receptor tyrosine kinase Tie2, is known to be involved in the regulation of embryonic lymphangiogenesis. However, the role of Ang-2 in postnatal pathological lymphangiogenesis, such as inflammation, is largely unknown. We used a combination of imaging, molecular, and cellular approaches to investigate whether Ang-2 is involved in inflammatory lymphangiogenesis. We observed strong and continuous expression of Ang-2 on newly generated lymphatic vessels for 2 wk in sutured corneas of BALB/c mice. This expression was concurrent with an increased number of lymphatic vessels. TNF-α expression also increased, with peak TNF-α expression occurring before peak Ang-2 expression was reached. In vitro experiments showed that TNF-α stimulates Ang-2 and Tie2 and ICAM-1 expression on human lymphatic endothelial cells (LECs) and blood vascular endothelial cells (BECs). Ang-2 alone did not affect the biological behavior of LECs, whereas Ang-2 combined with TNF-α significantly promoted the proliferation of LECs but not BECs. In mouse models, blockade of Ang-2 with L1-10, an Ang-2-specific inhibitor, significantly inhibited lymphangiogenesis but promoted angiogenesis. These results clearly indicate that Ang-2 acts as a crucial regulator of inflammatory lymphangiogenesis by sensitizing the lymphatic vasculature to inflammatory stimuli, thereby directly promoting lymphangiogenesis. The involvement of Ang-2 in inflammatory lymphangiogenesis provides a strong rationale for the exploitation of anti-Ang-2 treatment in the prevention and treatment of tumor metastasis and transplant rejection.

scholarly journals Thick Brain Slices Model the Ischemic Penumbra

1988 ◽  
Vol 8 (4) ◽  
pp. 586-597 ◽  
Author(s):  
George C. Newman ◽  
Frank E. Hospod ◽  
Priscilla Wu
Keyword(s):  
Glucose Utilization ◽  
Anaerobic Metabolism ◽  
Brain Slices ◽  
Ischemic Injury ◽  
Progressive Increase ◽  
Glycolytic Flux ◽  
Metabolic Profiles ◽  
Ischemic Penumbra ◽  
Morphologic Changes

Hypothalamic brain slices, varying in thickness from 400μ to 1,000μ, were assessed by studying 2-deoxyglucose (2DG) metabolism, lactate accumulation, inulin spaces, and morphology at the light and ultrastructural levels. Evidence of increased glycolytic flux due to anaerobic metabolism is found at thicknesses greater than 600μ in association with a progressive increase in the inulin-exclusion space. The metabolic profiles, as a function of depth into the slices, reveal that 700-μ slices function in a manner similar to 540-μ slices at the surfaces, but with a core of increased 2DG phosphorylation at the slice center. In contrast, the 1000-μ slices show significant reductions of 2DG and increases in 2DG6P relative to the 540-μ slices at the slice surface as well as in the slice interior, suggesting impaired transport of 2DG into cells and spread of ischemic injury from the slice interior to the slice surface. Despite these metabolic changes, only minor morphologic changes of ischemic injury were found at the center of thicker slices, and in vitro glucose utilization of 1000-μ slices remained constant for up to 15 h. These three slice thicknesses should provide a useful model for studying the neurochemistry and neuropharmacology of the ischemic penumbra.

scholarly journals Efficient In Vitro Generation of IL-22-Secreting ILC3 From CD34+ Hematopoietic Progenitors in a Human Mesenchymal Stem Cell Niche

2021 ◽  
Vol 12 ◽  
Author(s):  
Sabrina B. Bennstein ◽  
Sandra Weinhold ◽  
Özer Degistirici ◽  
Robert A. J. Oostendorp ◽  
Katharina Raba ◽  
...  
Keyword(s):  
Inflammatory Diseases ◽  
Transplant Rejection ◽  
Human Mesenchymal Stem Cells ◽  
Human Mesenchymal Stem Cell ◽  
Good Manufacturing Practice ◽  
Lymphoid Cells ◽  
Mucosal Barrier ◽  
Hematopoietic Progenitors ◽  
Surface Receptors

Innate lymphoid cells (ILCs) and in particular ILC3s have been described to be vital for mucosal barrier functions and homeostasis within the gastrointestinal (GI) tract. Importantly, IL-22-secreting ILC3 have been implicated in the control of inflammatory bowel disease (IBD) and were shown to reduce the incidence of graft-versus-host disease (GvHD) as well as the risk of transplant rejection. Unfortunately, IL-22-secreting ILC3 are primarily located in mucosal tissues and are not found within the circulation, making access to them in humans challenging. On this account, there is a growing desire for clinically applicable protocols for in vitro generation of effector ILC3. Here, we present an approach for faithful generation of functionally competent human ILC3s from cord blood-derived CD34+ hematopoietic progenitors on layers of human mesenchymal stem cells (MSCs) generated in good manufacturing practice (GMP) quality. The in vitro-generated ILC3s phenotypically, functionally, and transcriptionally resemble bona fide tissue ILC3 with high expression of the transcription factors (TF) RorγT, AHR, and ID2, as well as the surface receptors CD117, CD56, and NKp44. Importantly, the majority of ILC3 belonged to the desired effector subtype with high IL-22 and low IL-17 production. The protocol thus combines the advantages of avoiding xenogeneic components, which were necessary in previous protocols, with a high propensity for generation of IL-22-producing ILC3. The present approach is suitable for the generation of large amounts of ILC3 in an all-human system, which could facilitate development of clinical strategies for ILC3-based therapy in inflammatory diseases and cancer.

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