scholarly journals CELL-MEDIATED CYTOTOXICITY DURING REJECTION AND ENHANCEMENT OF ALLOGENEIC SKIN GRAFTS IN RATS

1972 ◽  
Vol 135 (6) ◽  
pp. 1301-1315 ◽  
Author(s):  
Hans-Hartmut Peter ◽  
Joseph D. Feldman
Keyword(s):  
Lymph Nodes ◽  
Thoracic Duct ◽  
Lymphoid Cells ◽  
Target Cells ◽  
Skin Grafts ◽  
Peak Activity ◽  
Adult Rats ◽  
Background Levels

Cell-mediated cytotoxicity (CMC) in spleens and lymph nodes of allografted rats was determined by release of 51Cr from labeled target cells incubated with aggressor lymphoid cells. CMC was first detected in grafted adult rats on day 5, peaked on days 7 and 8, and declined rapidly to background levels by days 9 to 11. In allografted neonates and in cyclophosphamide-treated or neonatally thymectomized adults CMC was a fraction of that observed in normal adult rats. Enhancing antibodies deferred in vivo peak activity of CMC in allografted neonates for 3–4 days, and blocked in vitro the action of aggressor lymphocytes by binding to target cells. Enhancing antibodies had no effect on the cytotoxicity of aggressor cells, but horse antibodies to rat thoracic duct cells inhibited in vitro CMC of aggressor cells.

Effect on the Sensitivity of Lymphoid Cells to Acriflavine after « in vivo » Treatment with Heterologous Albumin Coupled with Diazotized Acriflavin

1966 ◽  
Vol 52 (3) ◽  
pp. 177-185
Author(s):  
Aurelio Di Marco ◽  
Rosella Silvestrini ◽  
Emidio Calendi
Keyword(s):  
Lymph Nodes ◽  
Proliferative Activity ◽  
Lymphoid Cells ◽  
Low Doses ◽  
Proliferating Cells ◽  
In Vivo Treatment ◽  
Albino Mice ◽  
Different Doses

The possibility that the «in vivo» treatment with heterologous albumin coupled with diazotized acriflavine may affect the sensitivity of lymphoid cells to the action of acriflavine was studied. Albino mice CFW strain were treated subcutanceusly with the coupled albumin in the presence of complete Freund adjuvant. Lymph nodes from control and immunized animals, fifteen days after the treament, were cultured «in vitro» in the presence of different doses of acriflavine (from 0.5 to 4 μg/ml). The action of acriflavine was evaluated as the growth of cultures, the percent of lymphoid cells in the different phases of differentiation and the percent of proliferating cells after incubation for 24 hours in the presence of 3H thymidine. Results show that lymphoid cells of immunized mice are less sensitive to the citotoxic activity of acriflavine than those of the controls. Acriflavine, at low doses, reduces the growth of normal cultures and the proliferative activity of immature elements. At the highest doses the proliferation area is almost completely absent and the elements still present are strongly degenerated. Acriflavine, at the concentration able to reduce or to inhibit the growth of control cultures, is ineffective in altering the ratio of immature elements in cultures of immunized animals. The ability of these elements to incorporate 3H thymidine is also unchanged.

scholarly journals REJECTION OF TUMOR ALLOGRAFTS BY MOUSE SPLEEN CELLS SENSITIZED IN VITRO

1971 ◽  
Vol 133 (4) ◽  
pp. 821-833 ◽  
Author(s):  
Irun R. Cohen ◽  
Amiela Globerson ◽  
Michael Feldman
Keyword(s):  
Inhibitory Effect ◽  
Lymphoid Cells ◽  
Mouse Spleen ◽  
Target Cells ◽  
Functional Assay ◽  
Spleen Cells ◽  
Growth Of Tumor ◽  
Selection Of

This paper reports a model system of cellular immunity in which allosensitization of mouse spleen cells is induced in vitro. Allosensitization was achieved by culturing spleen cells upon monolayers of allogeneic fibroblasts. The ability of the spleen cells to inhibit the growth of tumor allografts in vivo served as a functional assay of sensitization. We found that unsensitized spleen cells or spleen cells sensitized against unrelated fibroblast antigens had no inhibitory effect on the growth of allogeneic fibrosarcoma cells when they were injected together into irradiated recipients. In contrast, spleen cells which were specifically allosensitized in vitro were found to be highly effective in inhibiting the growth of an equal number of allogeneic tumor cells. Several times more spleen cells from mice sensitized in vivo were required to produce a similar immune effect. This confirms the findings of previous studies which indicate that sensitization in cell culture can promote the selection of specifically sensitized lymphocytes. Preincubating sensitizing fibroblasts with allo-antisera blocked the allosensitization of spleen cells. This suggests that antibodies binding to fibroblasts may inhibit the induction of sensitization by competing with lymphocytes for antigenic sites. Mouse spleen cells which were able to recognize and reject tumor allografts in vivo were unable to cause lysis of target fibroblasts in vitro. Such fibroblasts, however, were susceptible to lysis by rat lymphoid cells sensitized by a similar in vitro method. These findings indicate that the conditions required for lymphocyte-mediated lysis of target cells may not be directly related to the processes of antigen recognition and allograft rejection in vivo.

scholarly journals THE ROLE OF LYMPHOCYTES IN THE SENSITIZATION OF RATS TO RENAL HOMOGRAFTS

1965 ◽  
Vol 122 (2) ◽  
pp. 347-360 ◽  
Author(s):  
S. Strober ◽  
J. L. Gowans
Keyword(s):  
Lymph Nodes ◽  
Thoracic Duct ◽  
Femoral Vein ◽  
F1 Hybrid ◽  
Duct Cells ◽  
Degree Of Sensitization ◽  
Spleen And Lymph Nodes

In order to study the role of blood-borne small lymphocytes in the sensitization of rats to renal homografts 2 techniques for the perfusion of isolated rat kidneys were employed: (a) the in vitro perfusion of kidneys with thoracic duct cells suspended in either an artificial medium or in blood; the perfusates were then injected into rats syngeneic with the lymphocyte donors; (b) the in vivo perfusion of kidneys with blood issuing from the femoral artery and returning to the femoral vein of living rats. The degree of sensitization conferred on the recipients by the perfusates was assessed by applying a skin homograft from the kidney donor and scoring the epithelial necrosis at 6 days. The in vitro experiments indicated that parental strain thoracic duct cells, which had passed through an F1 hybrid kidney could confer upon a parental rat sensitivity to an F1 skin graft. Several perfusions with radioactively labelled lymphocytes showed that the injected cells migrated to the lymph nodes and spleen of the recipients Labelled large pyroninophilic cells were occasionally seen in the spleen and lymph nodes of recipients, and it was suggested that these had arisen from the injected cells. Although the in vitro perfusions with blood indicated that renal homografts might sensitize their hosts within 1 hour, the in vivo perfusions suggested that about 5 to 12 hours were required. The more rapid sensitization in vitro was possibly due to the more frequent opportunity for contact between lymphocytes and kidney vascular endothelium which was afforded by the conditions in vitro.

scholarly journals Trajectory of chemical cocktail-induced neutrophil reprogramming

2020 ◽  
Vol 13 (1) ◽  
Author(s):  
Yi Zhou ◽  
Chuijin Wei ◽  
Shumin Xiong ◽  
Liaoliao Dong ◽  
Zhu Chen ◽  
...  
Keyword(s):  
Cell Types ◽  
Lymphoid Cells ◽  
Great Promise ◽  
Target Cells ◽  
Differentiation Potential ◽  
Hematopoietic Stem ◽  
Multipotent Progenitors ◽  
First Time

AbstractHematopoietic reprogramming holds great promise for generating functional target cells and provides new angle for understanding hematopoiesis. We reported before for the first time that diverse differentiated hematopoietic cell lineages could be reprogrammed back into hematopoietic stem/progenitor cell-like cells by chemical cocktail. However, the exact cell types of induced cells and reprogramming trajectory remain elusive. Here, based on genetic tracing method CellTagging and single-cell RNA sequencing, it is found that neutrophils could be reprogrammed into multipotent progenitors, which acquire multi-differentiation potential both in vitro and in vivo, including into lymphoid cells. Construction of trajectory map of the reprogramming procession shows that mature neutrophils follow their canonical developmental route reversely into immature ones, premature ones, granulocyte/monocyte progenitors, common myeloid progenitors, and then the terminal cells, which is stage by stage or skips intermediate stages. Collectively, this study provides a precise dissection of hematopoietic reprogramming procession and sheds light on chemical cocktail-induction of hematopoietic stem cells.

scholarly journals Inhibition of T-lymphocyte-mediated tumor-specific lysis by alloantisera directed against the H-2 serological specificities of the tumor

1975 ◽  
Vol 142 (4) ◽  
pp. 1023-1028 ◽  
Author(s):  
RN Germain ◽  
ME Dorf ◽  
B Benacerraf
Keyword(s):  
Lymphoid Cells ◽  
Target Cells ◽  
Cell Surface Antigens ◽  
Specific Lysis ◽  
Effector Cells ◽  
Experimental Systems ◽  
Major Histocompatibility Locus ◽  
Membrane Antigens

After appropriate in vivo or in vitro immunization, cytotoxic T lymphocytes (CTL) are generated which efficiently kill cells bearing particular membrane antigens in common with the immunizing cell (reviewed in reference 1). Such CTL have been most thoroughly studied in mice, employing alloimmunization with cells differing at the major histocompatibility locus, H-2. in such cases, the predominant cell surface antigens recognized by the CTL appear to be the molecules carrying the serologically defined H-2 specificities, coded for by the K and D regions of the H-2 complex (2). In other syngeneic models of cell-mediated specific cytolysis, involving lymphocyte chariomeningitis (LCM) virus- or ectromelia virus-infected cells or TNP-modified lymphoid cells, thymus-derived cells also constitute the main effector cell type. The CTL generated in these latter systems function most efficiently when virus-infected or TNP-modified target cells share identitites at the H-2K or H-2D loci with the effector CTL and stimulator cells (3-5). Another set of experimental systems in which CTL are generated and play a significant biological role is that of immunity to tumor-associated antigens (TAA) (6). The nature of the TAA which the CTL recognize is only beginning to be understood. Several recent reports indicated the existence of physiochemical and/or antigenic relationships between TAA and H-2 antigens (7,8). These relationships, together with the genetic restrictions cited above in the generation of CTL involving products of the H-2K or H-2D loci suggested the possibility that in certain tumor systems, the TAA which are able to most effectively stimulate CTL responses might be structurally similar to, or linked with, the H-2K or H- 2D molecules on the tumor surface. It has been previously demonstrated in allogenic models that antisera specific for the appropriate H-2K or H-2D products present on a target cell could specifically block CTL-mediated lysis (1,9). This report demonstrates that certain anti-H-2 alloantisera specific for the target tumor cells can block lysis of those target cells mediated by syngeneic tumor-specific CTL effector cells.

scholarly journals CELLULAR IMMUNOABSORBENTS IN TRANSPLANTATION IMMUNITY

1972 ◽  
Vol 135 (4) ◽  
pp. 972-984 ◽  
Author(s):  
Gideon Berke ◽  
Raphael H. Levey
Keyword(s):  
Tumor Growth ◽  
Tumor Cells ◽  
Lymphoid Cells ◽  
Target Cells ◽  
Transplantation Immunity

Mouse lymphoid cells, sensitized against tumor allografts, can be deprived of the immunoreactive cells by in vitro absorption with specific fibroblast monolayers. Populations of lymphocytes so depleted are less effective in retarding tumor growth in vivo and in lysing tumor cells in vitro. Moreover, the adsorbed immunoreactive cells can be recovered specifically and are subsequently efficient in inhibiting tumor growth in vivo and in killing tumor cells in vitro. Further evidence is presented for the suggestion that the destruction of target cells in vitro by sensitized lymphoid cells is truly representative of the mode of destruction of grafted cells in vivo.

scholarly journals Tumorigenicity and lysis by natural killers.

1981 ◽  
Vol 153 (1) ◽  
pp. 89-106 ◽  
Author(s):  
J L Collins ◽  
P Q Patek ◽  
M Cohn
Keyword(s):  
Protein Synthesis ◽  
Cell Lines ◽  
Fibroblast Cell ◽  
Lymphoid Cells ◽  
Target Cells ◽  
Nk Activity ◽  
Effector Cells ◽  
Resistant Cells

Detailed analysis of the natural killer (NK) activity directed at nontumorigenic cell lines and their transformed tumorigenic derivatives has revealed a paradox. On the one hand, a correlation has been found between the tumorigenic potential of chemically transformed fibroblast cell lines and their sensitivity to NK cells in vitro. Nontransformed cells (N-type cell lines) and cells tumorigenic in normal mice (C-type cell lines) are resistant to NK-mediated lysis. In contrast, cell lines that are tumorigenic in ATxFL mice (these mice are very low in NK activity), but not in normal mice (I-type cell lines) are sensitive to NK-mediated lysis. These findings support the concept that NK activity is involved in host surveillance against tumors. On the other hand, NK-resistant fibroblasts, whether taken directly form animals or derived as tumorigenic or nontumorigenic cell lines, compete with NK-sensitive target cells to inhibit their lysis by NK effectors. Not only are both NK-sensitive and -resistant cells recognized by NK effectors but both receive lytic signals from NK effector cells. Target cell resistance is a result of a protein synthesis-dependent mechanism that prevents lysis such that in the presence of inhibitors of protein synthesis all fibroblasts tested are NK sensitive. Those fibroblasts that are normally sensitive to NK-mediated lysis must be deficient in their ability to produce or respond to this counterlytic mechanism. These findings are in contrast with the general findings when lymphoid cells are studied as NK targets where sensitivity appears to be a result of recognition by NK effectors. Because our findings show that transformed and normal cells express the same recognition determinants, in order for NK activity to play an important in vivo role in tumor surveillance, a mechanism must operate to permit NK effectors to find their targets in vivo. In the absence of a special discrimination mechanism, the killing of NK-sensitive transformants that arise autochronously would be less than optimal as a consequence of competition by the normal, NK-resistant, cells.

scholarly journals STUDIES ON THE IN VIVO AND IN VITRO MULTIPLICATION OF THE LDH VIRUS OF MICE

1966 ◽  
Vol 123 (6) ◽  
pp. 985-998 ◽  
Author(s):  
Herman G. du Buy ◽  
Martin L. Johnson
Keyword(s):  
Lymph Nodes ◽  
Ascitic Fluid ◽  
Virus Titer ◽  
Electron Microscopic Observation ◽  
Peritoneal Macrophages ◽  
Virus Multiplication ◽  
Target Cells ◽  
Electron Microscopic

In vivo analysis of the virus titer in various loci, 24 hr after infection, showed that a titer similar to that in the blood plasma was found in the ascitic fluid of Erlich ascites cancer-bearing mice, and in lymph nodes, spleen, and thymus, i.e. loci which contain macrophages as a common cell type. However, only in the lymph nodes and in the ascitic fluid did the increase in virus titer precede or parallel the increase in the plasma. The LDH virus titer in the plasma of X-irradiated mice was similar to that of control mice, eliminating radiation-sensitive cells but not macrophages as target cells of the virus. Electron microscopic observation of infected lymph node cells revealed the presence of two types of particles: one consisting of small densely stained annuli, about 25 mµ in diameter and one of similar dense annuli with a halo extending the diameter to about 50 mµ. Such particles were repeatedly observed within single or double membraned vesicles. In vitro, the LDH virus multiplied only in cultures of mouse peritoneal macrophages, maintained in medium 199 with 10% FBS. The virus titer could be maintained for at least 33 days, during eleven serial passages, involving an overall dilution factor of 1011. These results corroborate the findings of Evans and Salaman, who used peritoneal macrophages maintained in Eagle's medium and 5 to 10% lamb serum. However, in the serial passage experiments reported here, the virus titer could only be maintained following trypsinization of each successive inoculum. The role of macrophages as the target cell for LDH virus multiplication in vivo is discussed.

Non-Viral Vectors for Gene Delivery

2018 ◽  
Vol 9 (1) ◽  
pp. 4-11 ◽  
Author(s):  
Aparna Bansal ◽  
Himanshu
Keyword(s):  
Gene Therapy ◽  
Viral Vectors ◽  
Transfection Efficiency ◽  
Gene Transfection ◽  
Expression System ◽  
Target Cells ◽  
Specific Expression ◽  
Naked Dna

Introduction: Gene therapy has emerged out as a promising therapeutic pave for the treatment of genetic and acquired diseases. Gene transfection into target cells using naked DNA is a simple and safe approach which has been further improved by combining vectors or gene carriers. Both viral and non-viral approaches have achieved a milestone to establish this technique, but non-viral approaches have attained a significant attention because of their favourable properties like less immunotoxicity and biosafety, easy to produce with versatile surface modifications, etc. Literature is rich in evidences which revealed that undoubtedly, non–viral vectors have acquired a unique place in gene therapy but still there are number of challenges which are to be overcome to increase their effectiveness and prove them ideal gene vectors. Conclusion: To date, tissue specific expression, long lasting gene expression system, enhanced gene transfection efficiency has been achieved with improvement in delivery methods using non-viral vectors. This review mainly summarizes the various physical and chemical methods for gene transfer in vitro and in vivo.

scholarly journals Combined In Vitro and In Vivo Approaches to Propose a Putative Adverse Outcome Pathway for Acute Lung Inflammation Induced by Nanoparticles: A Study on Carbon Dots

Nanomaterials ◽  
2021 ◽  
Vol 11 (1) ◽  
pp. 180
Author(s):  
Maud Weiss ◽  
Jiahui Fan ◽  
Mickaël Claudel ◽  
Luc Lebeau ◽  
Françoise Pons ◽  
...  
Keyword(s):  
Carbon Dots ◽  
Lung Inflammation ◽  
Adverse Outcome ◽  
Cellular Responses ◽  
Target Cells ◽  
Inflammasome Activation ◽  
Adverse Outcome Pathway ◽  
Acute Lung Inflammation

With the growth of nanotechnologies, concerns raised regarding the potential adverse effects of nanoparticles (NPs), especially on the respiratory tract. Adverse outcome pathways (AOP) have become recently the subject of intensive studies in order to get a better understanding of the mechanisms of NP toxicity, and hence hopefully predict the health risks associated with NP exposure. Herein, we propose a putative AOP for the lung toxicity of NPs using emerging nanomaterials called carbon dots (CDs), and in vivo and in vitro experimental approaches. We first investigated the effect of a single administration of CDs on mouse airways. We showed that CDs induce an acute lung inflammation and identified airway macrophages as target cells of CDs. Then, we studied the cellular responses induced by CDs in an in vitro model of macrophages. We observed that CDs are internalized by these cells (molecular initial event) and induce a series of key events, including loss of lysosomal integrity and mitochondrial disruption (organelle responses), as well as oxidative stress, inflammasome activation, inflammatory cytokine upregulation and macrophage death (cellular responses). All these effects triggering lung inflammation as tissular response may lead to acute lung injury.

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