Profiling the Resident and Infiltrating Monocyte/Macrophages during Rejection following Kidney Transplantation

Immune tolerance research is essential for kidney transplantation. Other than antibody and T cell-mediated immune rejection, macrophage-mediated innate immunity plays an important role in the onset phase of transplantation rejection. However, due to the complexity of the kidney environment as well as its diversity and low abundance, studies pertaining to monocyte/macrophages in kidney transplantation require further elucidation. In this study, kidney samples taken from healthy human adults and biopsy specimens from patients undergoing rejection following kidney transplantation were analysed and studied. By conducting a single-cell RNA analysis, the type and status of monocyte/macrophages in kidney transplantation were described, in which monocyte/macrophages were observed to form two different subpopulations: resident and infiltrating monocyte/macrophages. Furthermore, previously defined genes were mapped to all monocyte/macrophage types in the kidney and enriched the differential genes of the two main subpopulations using gene expression databases. Considering that various cases of rejection may be of the monocyte/macrophage type, the present data may serve as a reference for studies regarding immune tolerance following kidney transplantation.

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Relation between zinc content in saliva and blood in healthy human adults

Scandinavian Journal of Clinical and Laboratory Investigation ◽

10.3109/00365517709091509 ◽

1977 ◽

Vol 37 (5) ◽

pp. 469-472 ◽

Cited By ~ 13

Author(s):

A. Mathur ◽

K. Wallenius ◽

M. Abdulla

Keyword(s):

Zinc Content ◽

Healthy Human ◽

Human Adults

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Cardiovascular Effects of Exposure to Wood Smoke in Healthy Human Adults

Case Medical Research ◽

10.31525/ct1-nct04297761 ◽

2020 ◽

Author(s):

Keyword(s):

Cardiovascular Effects ◽

Wood Smoke ◽

Healthy Human ◽

Human Adults

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Reference tables with centiles of limb to body height ratios of healthy human adults for assessing potential thalidomide embryopathy

Anthropologischer Anzeiger ◽

10.1127/anthranz/2019/0981 ◽

2019 ◽

Vol 76 (5) ◽

pp. 391-400

Author(s):

Anna Reimann ◽

Rudolf Beyer ◽

Rebekka Mumm ◽

Christiane Scheffler

Keyword(s):

Body Height ◽

Healthy Human ◽

Human Adults

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Dehydroepiandrosterone Sulfate as a Digitalis Like Factor in Plasma of Healthy Human Adults

The Journal of Urology ◽

10.1016/s0022-5347(17)45809-5 ◽

1986 ◽

Vol 135 (3) ◽

pp. 664-664

Author(s):

S. Vasdev ◽

L. Longerich ◽

E. Johnson ◽

D. Brent ◽

M.H. Gault

Keyword(s):

Dehydroepiandrosterone Sulfate ◽

Healthy Human ◽

Human Adults

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Safety and immunogenicity of intranasal murine parainfluenza virus type 1 (Sendai virus) in healthy human adults

Vaccine ◽

10.1016/j.vaccine.2004.01.053 ◽

2004 ◽

Vol 22 (23-24) ◽

pp. 3182-3186 ◽

Cited By ~ 97

Author(s):

Karen S Slobod ◽

Jerry L Shenep ◽

Jorge Luján-Zilbermann ◽

Kim Allison ◽

Brita Brown ◽

...

Keyword(s):

Virus Type ◽

Sendai Virus ◽

Parainfluenza Virus ◽

Healthy Human ◽

Human Adults

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Behavioral and cognitive effects of tyrosine intake in healthy human adults

Pharmacology Biochemistry and Behavior ◽

10.1016/j.pbb.2015.03.008 ◽

2015 ◽

Vol 133 ◽

pp. 1-6 ◽

Cited By ~ 10

Author(s):

Adrian Hase ◽

Sophie E. Jung ◽

Marije aan het Rot

Keyword(s):

Cognitive Effects ◽

Healthy Human ◽

Human Adults

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Abstract 16582: Costimulation Blockade With Anti Cd80 and Cd86 Monoclonal Antibodies Prolonged Graft Survival in Allogeneic Ips Cell-Derived Cardiomyocyte Patch Transplantation

Circulation ◽

10.1161/circ.142.suppl_3.16582 ◽

2020 ◽

Vol 142 (Suppl_3) ◽

Author(s):

Masaro Nakae ◽

Shigeru Miyagawa ◽

Takuji Kawamura ◽

Koichiro Uchida ◽

Ko Okumura ◽

...

Keyword(s):

Monoclonal Antibodies ◽

T Cell ◽

Graft Survival ◽

Immune Tolerance ◽

Immune Rejection ◽

Mice Model ◽

Ips Cell ◽

T Cell Anergy ◽

Cell Anergy ◽

Costimulatory Pathway

Introduction: How to avoid immune rejection after transplantation should be elucidated for confirmed efficacy in clinical application of allogenic induced pluripotent stem cell derived cardiomyocyte patch. The blockade of CD28-CD80/86 costimulation is known to induce T cell anergy and immune tolerance by the recruitment of regulatory T cells (T reg) and prolong graft survival in organ transplantation. Hypothesis: We hypothesized that the blockade of CD28-CD80/CD86 costimulatory pathway by anti-CD80/CD86 monoclonal antibodies (mAbs) induces T cell anergy in vivo and suppresses immune rejection in allogeneic iPSC-CMs subcutaneous transplantation mice model. Methods: T cell anergy was induced in vitro by co-culture of Balb/c and 25Gy irradiated C57BL/6 splenocytes with anti-CD80/86 mAbs for 5 days. The inhibitory effect of anergic cells was evaluated by mixed lymphocyte reaction (MLR) in C57BL/6 and Balb/c splenocytes with anergic cells. IFN-g in MLR supernatants was measured by ELISAs to assess immune response. C57BL/6 iPSC-CMs expressing luciferase were subcutaneously transplanted into Balb/c. Anti-CD80/CD86 mAbs were injected intraperitoneally 250μg/dose on day 0, 1, and 2 (treated mice, n=6). In control mice (n=6), equivalent volume of saline was injected. To evaluate iPSC-CMs graft survival, photon counts of iPSC-CMs were measured by bioluminescence imaging system (BLI). Cells of harvested grafts were analyzed by immunofluorescence staining (IF). Results: On ELISAs, IFN-g in MLR supernatants co-cultured with anergic cells was significantly lower as compared with those without anergic cells (12.3±14.4 vs. 251±80.2 pg/ml, p=0.007). The ability to suppress the alloresponses was dose-dependent. BLI showed that photon counts on day 14 in treated mice were significantly higher than in control mice (7397±2651 vs. 2703±1271, p=0.003). IF showed a siginificantly higher ratio of CD4 and Foxp3 double positive cells to CD4-postive cells in the grafts on day 7 in treated mice as compared with in control mice (23±3% vs. 9±3%, p=0.009) Conclusions: The blockade of CD28-CD80/CD86 costimulatory pathway might suppress immune rejection in allogeneic iPSC-CMs transplantation mice model and T reg might involve this immune tolerance.

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