Evidence map›Paper›PMID 31764762›Full record

ArticleTransplantation2020

In Vivo Analysis of Human Immune Responses in Immunodeficient Rats.

Séverine Ménoret, Laure-Hélène Ouisse, Laurent Tesson, Séverine Remy, Claire Usal, Aude Guiffes, Vanessa Chenouard, Pierre-Joseph Royer, Gwenaelle Evanno, Bernard Vanhove and 2 more

Abstract read
In one paragraph

Article in Transplantation, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.

0numbers the graph read from it
0cells of the map it votes in
18citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

18 citing papers in PubMed.

  1. Humanized immune system animal models and their recent applications.Animal models and experimental medicine · 2026
    Review
  2. Review
  3. Article
  4. Review
  5. Article
  6. Review
  7. Xenogeneic Animal Models of Graft-Versus-Host Disease.Methods in molecular biology (Clifton, N.J.) · 2025
    Article
  8. Article
  9. Article
  10. Rat Models of Hormone Receptor-Positive Breast Cancer.Journal of mammary gland biology and neoplasia · 2024
    Review
  11. Article
  12. Review
  13. Article
  14. Article
  15. Review
  16. Review
  17. Review
  18. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

12 authors.

Séverine MénoretCentre de Recherche en Transplantation et Immunologie UMR1064, INSERM, Université de Nantes, Nantes, France.
Laure-Hélène OuisseCentre de Recherche en Transplantation et Immunologie UMR1064, INSERM, Université de Nantes, Nantes, France.
Laurent TessonCentre de Recherche en Transplantation et Immunologie UMR1064, INSERM, Université de Nantes, Nantes, France.
Séverine RemyCentre de Recherche en Transplantation et Immunologie UMR1064, INSERM, Université de Nantes, Nantes, France.
Claire UsalCentre de Recherche en Transplantation et Immunologie UMR1064, INSERM, Université de Nantes, Nantes, France.
Aude GuiffesCentre de Recherche en Transplantation et Immunologie UMR1064, INSERM, Université de Nantes, Nantes, France.
Vanessa ChenouardCentre de Recherche en Transplantation et Immunologie UMR1064, INSERM, Université de Nantes, Nantes, France.
Pierre-Joseph RoyerXenothera, Nantes, France.
Gwenaelle EvannoXenothera, Nantes, France.
Bernard VanhoveXenothera, Nantes, France.
Eliane PiaggioPSL Research University, Institut Curie Research Center, INSERM U932, Paris, France.
Ignacio AnegonCentre de Recherche en Transplantation et Immunologie UMR1064, INSERM, Université de Nantes, Nantes, France.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundHumanized immune system immunodeficient mice have been extremely useful for the in vivo analyses of immune responses in a variety of models, including organ transplantation and graft versus host disease (GVHD) but they have limitations. Rat models are interesting complementary alternatives presenting advantages over mice, such as their size and their active complement compartment. Immunodeficient rats have been generated but human immune responses have not yet been described.

methodsWe generated immunodeficient Rat Rag-/- Gamma chain-/- human signal regulatory protein alpha-positive (RRGS) rats combining Rag1 and Il2rg deficiency with the expression of human signal regulatory protein alpha, a negative regulator of macrophage phagocytosis allowing repression of rat macrophages by human CD47-positive cells. We then immune humanized RRGS animals with human peripheral blood mononuclear cells (hPBMCs) to set up a human acute GVHD model. Treatment of GVHD was done with a new porcine antihuman lymphocyte serum active through complement-dependent cytotoxicity. We also established a tumor xenograft rejection model in these hPBMCs immune system RRGS animals by subcutaneous implantation of a human tumor cell line.

resultsRRGS animals receiving hPBMCs showed robust and reproducible reconstitution, mainly by T and B cells. A dose-dependent acute GVHD process was observed with progressive weight loss, tissue damage, and death censoring. Antihuman lymphocyte serum (L1S1) antibody completely prevented acute GVHD. In the human tumor xenograft model, detectable tumors were rejected upon hPBMCs injection.

conclusionshPBMC can be implanted in RRGS animals and elicit acute GVHD or rejection of human tumor cells and these are useful models to test new immunotherapies.

Indexed as

Immunocompromised HostAnimalsAntigens, DifferentiationAntilymphocyte SerumBreast NeoplasmsCell Line, TumorDisease Models, AnimalFemaleGraft vs Host DiseaseHeterograftsHomeodomain ProteinsHumansImmunoglobulin gamma-ChainsImmunologic Deficiency SyndromesLeukocytes, MononuclearRats, Sprague-DawleyAntigens, DifferentiationAntilymphocyte SerumHomeodomain ProteinsImmunoglobulin gamma-ChainsRAG-1 proteinReceptors, ImmunologicSIRPA protein, human

Identifiers

PMID31764762
PMCPMC7147402

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.