scholarly journals Disruption of Tfh:B Cell Interactions Prevents Antibody-Mediated Rejection in a Kidney Transplant Model in Rats: Impact of Calcineurin Inhibitor Dose

2021 ◽  
Vol 12 ◽  
Author(s):  
Louisa Steines ◽  
Helen Poth ◽  
Antonia Schuster ◽  
Kerstin Amann ◽  
Bernhard Banas ◽  
...  
Keyword(s):  
Kidney Transplant ◽  
Cyclosporine A ◽  
Plasma Cells ◽  
Rat Kidney ◽  
Cell Interactions ◽  
High Dose ◽  
Humoral Immune ◽  
Antibody Mediated Rejection ◽  
Follicular Helper ◽  
Transplant Model

We aimed to investigate the mechanisms of humoral immune activation in ABMR using a MHC-mismatched rat kidney transplant model. We applied low dose cyclosporine A (loCNI) to allow donor-specific antibody (DSA) formation and rejection and high dose cyclosporine A (hiCNI) for non-rejection. DSA and leukocyte subsets were measured by flow cytometry. Germinal centers (GC), T follicular helper cells (Tfh), plasma cells and interleukin-21 (IL-21) expression were analyzed by immunofluorescence microscopy. Expression of important costimulatory molecules and cytokines was measured by qRT-PCR. Allograft rejection was evaluated by a nephropathologist. We found that DSA formation correlated with GC frequency and expansion, and that GC size was linked to the number of activated Tfh. In hiCNI, GC and activated Tfh were virtually absent, resulting in fewer plasma cells and no DSA or ABMR. Expression of B cell activating T cell cytokine IL-21 was substantially inhibited in hiCNI, but not in loCNI. In addition, hiCNI showed lower expression of ICOS ligand and IL-6, which stimulate Tfh differentiation and maintenance. Overall, Tfh:B cell crosstalk was controlled only by hiCNI treatment, preventing the development of DSA and ABMR. Additional strategies targeting Tfh:B cell interactions are needed for preventing alloantibody formation and ABMR.

scholarly journals CD47 Blockade Reduces Ischemia-Reperfusion Injury and Improves Outcomes in a Rat Kidney Transplant Model

2014 ◽  
Vol 98 (4) ◽  
pp. 394-401 ◽  
Author(s):  
Yiing Lin ◽  
Pamela T. Manning ◽  
Jianluo Jia ◽  
Joseph P. Gaut ◽  
Zhenyu Xiao ◽  
...  
Keyword(s):  
Reperfusion Injury ◽  
Kidney Transplant ◽  
Ischemia Reperfusion Injury ◽  
Rat Kidney ◽  
Ischemia Reperfusion ◽  
Transplant Model

Evaluation of a Novel Cold Storage Solution (HBS) in a Rat Kidney Transplant Model

2007 ◽  
Vol 20 (4) ◽  
pp. 257-263 ◽  
Author(s):  
Fernando Lopez-Neblina ◽  
Alexander H. Toledo ◽  
Luis H. Toledo-Pereyra
Keyword(s):  
Kidney Transplant ◽  
Cold Storage ◽  
Rat Kidney ◽  
Transplant Model ◽  
Storage Solution

Low-dose cyclosporine mediates donor hyporesponsiveness in a fully mismatched rat kidney transplant model

2012 ◽  
Vol 26 (4) ◽  
pp. 176-185 ◽  
Author(s):  
Christian Denecke ◽  
Anja Reutzel-Selke ◽  
Birgit Sawitzki ◽  
Olaf Boenisch ◽  
Zain Khalpey ◽  
...  
Keyword(s):  
Kidney Transplant ◽  
Low Dose ◽  
Rat Kidney ◽  
Transplant Model

scholarly journals MP76-03 KIDNEY GRAFT DAMAGE AFTER LONG COLD ISCHEMIA TIME IS ATTENUATED BY RECOMBINANT THROMBOMODULIN ALPHA IN A RAT KIDNEY TRANSPLANT MODEL

2019 ◽  
Vol 201 (Supplement 4) ◽  
Author(s):  
Satoshi Tamaki* ◽  
Kazunobu Shinoda ◽  
Masayuki Shimoda ◽  
Shinya Morita ◽  
Ryohei Takahashi ◽  
...  
Keyword(s):  
Kidney Transplant ◽  
Rat Kidney ◽  
Kidney Graft ◽  
Cold Ischemia Time ◽  
Cold Ischemia ◽  
Ischemia Time ◽  
Recombinant Thrombomodulin ◽  
Transplant Model

scholarly journals Regulatory T-cells are central hubs for age-, sex- and severity-associated cellular networks during COVID-19

2022 ◽  
Author(s):  
Jonas Søndergaard ◽  
Janyerkye Tulyeu ◽  
Ryuya Edahiro ◽  
Yuya Shira ◽  
Yuta Yamaguchi ◽  
...  
Keyword(s):  
T Cells ◽  
Regulatory T Cells ◽  
Cellular Networks ◽  
Humoral Immunity ◽  
Plasma Cells ◽  
Humoral Immune ◽  
Follicular Helper ◽  
Wide Range ◽  
Male Patients ◽  
Critical Patients

Using single-cell proteomics by mass cytometry, we investigate changes to a broad selection of over 10,000,000 immune cells in a cohort of moderate, severe, and critical Japanese COVID-19 patients and healthy controls with a particular focus on regulatory T-cells (Tregs). We find significant disruption within all compartments of the immune system and the emergence of atypical CTLA-4high CD4 T-cells and proliferating HLA-DRlowCD38high Tregs associated with critical patients. We also observed disrupted regulation of humoral immunity in COVID-19, with a loss of circulating T follicular regulatory T cells (Tfr) and altered T follicular helper (Tfh)/Tfr and plasma cell/Tfr ratios, all of which are significantly lower in male patients. Shifting ratios of CXCR4 and CXCR5 expression in B-cells provides further evidence of an autoimmune phenotype and dysregulated humoral immunity. These results suggest that Tregs are central to the changing cellular networks of a wide range of cells in COVID-19 and that sex specific differences to the balance of Tfr, Tfh and plasma cells may have important implications for the specificity of the humoral immune response to SARS-CoV-2.

Synergism of CTLA4-IG and anti-CD4 monoclonal antibody treatment in a rat kidney transplant model

1997 ◽  
Vol 29 (1-2) ◽  
pp. 1307-1309 ◽  
Author(s):  
E. Graser ◽  
K. Risch ◽  
P.S. Linsley ◽  
W.W. Hancock ◽  
J. Brock ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
Kidney Transplant ◽  
Rat Kidney ◽  
Antibody Treatment ◽  
Monoclonal Antibody Treatment ◽  
Transplant Model

scholarly journals The origins, function, and regulation of T follicular helper cells

2012 ◽  
Vol 209 (7) ◽  
pp. 1241-1253 ◽  
Author(s):  
Cindy S. Ma ◽  
Elissa K. Deenick ◽  
Marcel Batten ◽  
Stuart G. Tangye
Keyword(s):  
B Cells ◽  
Plasma Cells ◽  
Natural Infection ◽  
Critical Role ◽  
Cell Formation ◽  
T Follicular Helper Cells ◽  
Humoral Immune ◽  
Helper Cells ◽  
Follicular Helper ◽  
Immunological Diseases

The generation of high-affinity antibodies (Abs) plays a critical role in the neutralization and clearance of pathogens and subsequent host survival after natural infection with a variety of microorganisms. Most currently available vaccines rely on the induction of long-lived protective humoral immune responses by memory B cells and plasma cells, underscoring the importance of Abs in host protection. Ab responses against most antigens (Ags) require interactions between B cells and CD4+ T helper cells, and it is now well recognized that T follicular helper cells (Tfh) specialize in providing cognate help to B cells and are fundamentally required for the generation of T cell–dependent B cell responses. Perturbations in the development and/or function of Tfh cells can manifest as immunopathologies, such as immunodeficiency, autoimmunity, and malignancy. Unraveling the cellular and molecular requirements underlying Tfh cell formation and maintenance will help to identify molecules that could be targeted for the treatment of immunological diseases that are characterized by insufficient or excessive Ab responses.

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