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Salim Hamdani, Allan Thiolat, Sina Naserian, Cynthia Grondin, Stéphane Moutereau, Anne Hulin, Julien Calderaro, Philippe Grimbert, José Laurent Cohen, Daniel Azoulay, Caroline Pilon
AIM: To test whether a delayed and short course of rapamycin would induce immunosuppressive effects following allogeneic orthotopic liver transplantation (OLT) in rats. METHODS: Allogeneic OLTs were performed using Dark Agouti livers transplanted into Lewis recipients, and syngeneic OLTs were performed using the Lewis rat strain. Rapamycin (1 mg/kg per day) was administered by gavage from day 4 to day 11 post-transplantation. Lymphocyte cellular compartments were analyzed by flow cytometry in draining lymph nodes, non-draining lymph nodes and the spleen at days 11 and 42 in rapamycin-treated rats, untreated control rats and syngeneic grafted rats...
October 14, 2017: World Journal of Gastroenterology: WJG
Nevena Arsenović-Ranin, Duško Kosec, Ivan Pilipović, Mirjana Nacka-Aleksić, Biljana Bufan, Zorica Stojić-Vukanić, Gordana Leposavić
The study examined the influence of age, sex and peripubertal gonadectomy on a set of T-cell phenotypic parameters. Rats of both sexes were gonadectomised at the age of 1 month and peripheral blood and spleen T lymphocytes from non-gonadectomised and gonadectomised 3- and 11-month-old rats were examined for the expression of differentiation/activation (CD90/CD45RC) and immunoregulatory markers. Peripheral blood T lymphocytes from non-gonadectomised rats showed age-dependent sexual dimorphisms in (1) total count (lower in female than male 11-month-old rats); (2) CD4+:CD8 + cell ratio (higher in female than male rats of both ages); (3) the proportion of recent thymic emigrants in CD8 + T cells (lower in female than male 3-month-old rats) and (4) the proportions of mature naïve and memory/activated cells (irrespective of age, the proportion of naïve cells was higher, whereas that of memory/activated cells was lower in females)...
July 2017: Molecular and Cellular Biochemistry
Elodie Picarda, Séverine Bézie, Laetitia Boucault, Elodie Autrusseau, Stéphanie Kilens, Dimitri Meistermann, Bernard Martinet, Véronique Daguin, Audrey Donnart, Eric Charpentier, Laurent David, Ignacio Anegon, Carole Guillonneau
Rat and human CD4+ and CD8+ Tregs expressing low levels of CD45RC have strong immunoregulatory properties. We describe here that human CD45 isoforms are nonredundant and identify distinct subsets of cells. We show that CD45RC is not expressed by CD4+ and CD8+ Foxp3+ Tregs, while CD45RA/RB/RO are. Transient administration of a monoclonal antibody (mAb) targeting CD45RC in a rat cardiac allotransplantation model induced transplant tolerance associated with inhibition of allogeneic humoral responses but maintained primary and memory responses against cognate antigens...
February 9, 2017: JCI Insight
Séverine Bézie, Elodie Picarda, Jason Ossart, Bernard Martinet, Ignacio Anegon, Carole Guillonneau
In transplantation tolerance, numerous regulatory populations have the capacity to inhibit allograft rejection; however, their compensatory capacities have never been clearly evidenced. We have previously demonstrated that the tolerogenic effect mediated by CD8(+)CD45RC(low) regulatory T cells (Tregs) in a model of organ transplantation with CD40Ig could be abrogated by permanent depletion of CD8(+) cells that resulted in allograft rejection in half of the recipients. This result demonstrated that CD8(+) Tregs were essential, but also that half of the recipients still survived indefinitely...
December 15, 2015: Journal of Immunology: Official Journal of the American Association of Immunologists
Mirjana Nacka-Aleksić, Jasmina Djikić, Ivan Pilipović, Zorica Stojić-Vukanić, Duško Kosec, Biljana Bufan, Nevena Arsenović-Ranin, Mirjana Dimitrijević, Gordana Leposavić
Compared with females, male Dark Agouti (DA) rats immunized for experimental autoimmune encephalomyelitis (EAE) with rat spinal cord homogenate in complete Freund's adjuvant (CFA) exhibited lower incidence of the disease, but the maximal neurological deficit was greater in the animals that developed the disease. Consistently, at the peak of the disease greater number of reactivated CD4+CD134+CD45RC- T lymphocytes was retrieved from male rat spinal cord. Their microglia/macrophages were more activated and produced greater amount of prototypic proinflammatory cytokines in vitro...
October 2015: Brain, Behavior, and Immunity
Marek Sinkora, Jana Sinkorova
A course and a site of B cell development in swine are not firmly known. In this study, we show that B cell lymphogenesis is located in the bone marrow (BM). According to expression of MHC class II (MHC-II), CD2, CD21, CD25, CD45RC, CD172a, swine workshop cluster (identification number) (SWC) 7, and μHC, porcine BM cells were resolved into seven subsets representing sequential stages of development. Profile of rearrangement-specific products and transcripts from sorted BM cells confirmed the proposed developmental pathway...
November 15, 2014: Journal of Immunology: Official Journal of the American Association of Immunologists
Patricia Jacobo, Vanesa A Guazzone, Cecilia V Pérez, Livia Lustig
PROBLEM: The phenotype and function of regulatory T (Treg) cells in rats with experimental autoimmune orchitis (EAO) was evaluated. METHOD OF STUDY: Distribution of Treg cells in draining lymph nodes from the testis (TLN) and from the site of immunization (ILN) was analysed by immunohistochemistry. The number, phenotype and proliferative response (5-bromo-2'-deoxyuridine incorporation) of Treg cells were evaluated by flow cytometry and Treg cell suppressive activity by in vitro experiments...
February 2015: American Journal of Reproductive Immunology: AJRI
Z-L Yang, K Cheng, H G Sun, W W Zou, M M Wu
In this study, early expressions of peripheral blood Th1 and Th2 cells were documented following rat liver transplantation and related to immune status. Rats were divided into 3 groups: group A (control): syngeneic transplantation (Brown Norway (BN) → BN); group B: allogeneic transplantation + cyclosporine A (CsA); group C: allogeneic transplantation (Lewis → BN). Flow cytometry was used to analyze peripheral blood CD4(+)CD45RC percentage on days 1, 3, 5, 7, and 14 following transplantation, and were compared to graft rejection pathological grades and receptor survival times...
2013: Genetics and Molecular Research: GMR
Nevena Arsenović-Ranin, Milica Perišic, Biljana Bufan, Zorica Stojić-Vukanić, Ivan Pilipović, Duško Kosec, Gordana Leposavić
The study was undertaken to assess the effects of ovarian hormone withdrawal in prepubertal age on thymopoiesis in 2- (young) and 11-month-old (middle-aged) rats. In ovariectomized (Ox) rats, irrespective of age, thymic weight and cellularity were greater than in age-matched controls, but the values of both parameters exhibited the age-related decline. In addition, although thymopoietic efficiency was increased in both groups of Ox rats when compared with age-matched controls, thymopoiesis exhibited the age-related decline mirrored in the lower numbers of both CD4+ and CD8+ recent thymic emigrants in peripheral blood...
June 2013: Experimental Biology and Medicine
Laurence Ordonez, Isabelle Bernard, Marianne Chabod, Jean-François Augusto, Valerie Lauwers-Cances, Christelle Cristini, Maria-Cristina Cuturi, Jean-François Subra, Abdelhadi Saoudi
Although transplantation is the common treatment for end-stage renal failure, allograft rejection and marked morbidity from the use of immunosuppressive drugs remain important limitations. A major challenge in the field is to identify easy, reliable and noninvasive biomarkers allowing the prediction of deleterious alloreactive immune responses and the tailoring of immunosuppressive therapy in individuals according to the rejection risk. In this study, we first established that the expression of the RC isoform of the CD45 molecule (CD45RC) on CD4 and CD8 T cells from healthy individuals identifies functionally distinct alloreactive T cell subsets that behave differently in terms of proliferation and cytokine secretion...
2013: PloS One
C Pedros, O Papapietro, C Colacios, A Casemayou, I Bernard, V Garcia, D Lagrange, B Mariamé, O Andreoletti, G J Fournié, A Saoudi
Gold or mercury salts trigger a dramatic IgE response and a CD4 T-cell-dependent nephropathy in Brown-Norway (BN), but not in Lewis (LEW) rats. We previously identified the 1.1-Mb Iresp3 (immunoglobin response QTL3) locus on chromosome 9 that controls these gold salt-triggered immune disorders. In the present work, we investigated the genetic control of HgCl(2)-induced immunological disorders and assessed the relative contribution of the CD45RC(high) and CD45RC(low) CD4 T-cell subpopulations in this control...
June 2013: Genes and Immunity
Stephanie C Talker, Tobias Käser, Katharina Reutner, Corinna Sedlak, Kerstin H Mair, Hanna Koinig, Robert Graage, Miriam Viehmann, Eva Klingler, Andrea Ladinig, Mathias Ritzmann, Armin Saalmüller, Wilhelm Gerner
Detailed information concerning the development of the immune system in young pigs is still rudimental. In the present study, we analyzed changes in phenotype and absolute numbers of natural killer cells, γδ T cells, T helper cells, regulatory T cells and cytolytic T cells in the blood of pigs from birth to six months of age. For each lymphocyte subpopulation, a combination of lineage and differentiation markers was investigated by six-color flow cytometry. Major findings were: (i) absolute numbers of γδ T cells strongly increased from birth until 19-25 weeks of age, indicating an important role for these cells during adolescence; (ii) phenotype of T helper cells changed over time from CD8α(-)SLA-DR(-)CD27(+) towards CD8α(+)SLA-DR(+)CD27(-) but CD45RC(-) T helper cells were found immediately after birth, therefore questioning the role of this marker for the identification of T-helper memory cells; (iii) for cytolytic T cells, putative phenotypes for early effector (CD3(+)CD8αβ(+)perforin(+)CD27(dim)) and late effector or memory cells (CD3(+)CD8αβ(+)perforin(+)CD27(-)) could be identified...
May 2013: Developmental and Comparative Immunology
M A Birchall, S M Ayling, R Harley, P J Murison, R Burt, L Mitchard, A Jones, P Macchiarini, C R Stokes, M Bailey
Despite recent tissue-engineering advances, there is no effective way of replacing all the functions of the larynx in those requiring laryngectomy. A recent clinical transplant was a success. Using quantitative immunofluorescence targeted at immunologically relevant molecules, we have studied the early (48 h and 1 week) immunological responses within larynxes transplantated between seven pairs of National Institutes of Health (NIH) minipigs fully homozygous at the major histocompatibility complex (MHC) locus...
March 2012: Clinical and Experimental Immunology
A Kovšca Janjatović, G Lacković, F Božić, D Spoljarić, M Popović, H Valpotić, N Vijtiuk, Z Pavičić, I Valpotić
Colidiarrhea and colienterotoxemia caused by F4(+) and/or F18(+) enterotoxigenic E. coli (ETEC) strains are the most prevalent infections of suckling and weaned pigs. Here we tested the immunogenicity and protective effectiveness of attenuated F18ac(+) non-ETEC vaccine candidate strain against challenge infection with F4ac(+) ETEC strain by quantitative phenotypic analysis of small intestinal leukocyte subsets in weaned pigs.We also evaluated levamisole as an immune response modifier (IRM) and its adjuvanticity when given in the combination with the experimental vaccine...
December 29, 2009: European Journal of Histochemistry: EJH
Elodie Picarda, Ignacio Anegon, Carole Guillonneau
Recent studies in the field of CD8(+) Tregs have allowed a better identification and characterization of this subset of regulatory cells. Their key role in the regulation of allogeneic responses is now well established. To take full advantage of CD8(+) Treg cells in future therapeutic applications, a better knowledge is required, particularly concerning the contribution of the T-cell receptor (TCR) in cell function as well as the role and importance of its antigenic specificity. Here, we focused on the CD8(+)CD45RC(low) Tregs, which in rats induce an indefinite long-term allograft acceptance...
April 2011: Immunotherapy
Toshitake Hyodo, Takashi Oda, Yuichi Kikuchi, Keishi Higashi, Taketoshi Kushiyama, Kojiro Yamamoto, Muneharu Yamada, Shigenobu Suzuki, Ryota Hokari, Manabu Kinoshita, Shuhji Seki, Hidehiko Fujinaka, Tadashi Yamamoto, Soichiro Miura, Hiroo Kumagai
The voltage-gated potassium channel Kv1.3 has been recently identified as a molecular target that allows the selective pharmacological suppression of effector memory T cells (T(EM)) without affecting the function of naïve T cells (T(N)) and central memory T cells (T(CM)). We found that Kv1.3 was expressed on glomeruli and some tubules in rats with anti-glomerular basement membrane glomerulonephritis (anti-GBM GN). A flow cytometry analysis using kidney cells revealed that most of the CD4(+) T cells and some of the CD8(+) T cells had the T(EM) phenotype (CD45RC(-)CD62L(-))...
December 2010: American Journal of Physiology. Renal Physiology
A Kovsca Janjatović, G Lacković, F Bozić, D Kezić, M Popović, H Valpotić, I Harapin, Z Pavicić, B Njari, I Valpotić
Enterotoxigenic Escherichia coli (ETEC) infection is the most common type of porcine postweaning colibacillosis (PWC). Among fimbriae of porcine ETEC strains the best studied family of fimbriae are the members of F4 adhesins, existing in at least three variants: ab, ac, ad. Active immunization against porcine PWC is difficult due to: i) ETEC strains are only one of the essential predisposing factors, ii) the success of vaccinal antigen uptake depends on the presence of enterocyte receptors for F4 adhesins, iii) the intestinal immune system may react with tolerance or hypersensitivity to the same antigens depending on the dose and form of the vaccinal immunogen, and iv) kinetics of the specific immune responses may be different in the case of F4 (earlier) and the other ETEC adhesins, particularly F18 (later)...
January 2010: European Journal of Histochemistry: EJH
A Kovsca Janjatovic, G Lackovic, F Bozic, D Spoljaric, M Popovic, H Valpotic, N Vijtiuk, Z Pavicic, I Valpotic
Colidiarrhea and colienterotoxemia caused by F4+ and/or F18+ enterotoxigenic E. coli (ETEC) strains are the most prevalent infections of suckling and weaned pigs. Here we tested the immunogenicity and protective effectiveness of attenuated F18ac+ non- ETEC vaccine candidate strain against challenge infection with F4ac+ ETEC strain by quantitative phenotypic analysis of small intestinal leukocyte subsets in weaned pigs.We also evaluated levamisole as an immune response modifier (IRM) and its adjuvanticity when given in the combination with the experimental vaccine...
October 2009: European Journal of Histochemistry: EJH
Yuta Abe, Hidejiro Urakami, Dmitry Ostanin, Gazi Zibari, Tetsu Hayashida, Yuko Kitagawa, Matthew B Grisham
BACKGROUND: Donor-specific blood transfusion (DST) prior to solid organ transplantation has been shown to induce long-term allograft survival in the absence of immunosuppressive therapy. Although the mechanisms underlying DST-induced allograft tolerance are not well defined, there is evidence to suggest DST induces one or more populations of antigen-specific regulatory cells that suppress allograft rejection. However, neither the identity nor the regulatory properties of these tolerogenic lymphocytes have been reported...
2009: PloS One
Laurence Ordonez, Isabelle Bernard, Fatima-Ezzahra L'faqihi-Olive, Jan Willem Cohen Tervaert, Jan Damoiseaux, Abdelhadi Saoudi
In animal models of anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV), the proportion of CD45RC T cell subsets is important for disease susceptibility. Their human counterparts are, however, functionally ill defined. In this report, we studied their distribution in healthy controls (HC), AAV patients and in Systemic lupus erythematous (SLE) patients as disease controls. We showed that CD45RC expression level on human CD4 and CD8 T cells identifies subsets that are highly variable among individuals...
2009: PloS One
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