CD28 Family and Chronic Rejection: “To Belatacept...and Beyond!”

Kidneys are one of the most frequently transplanted human organs. Immunosuppressive agents may prevent or reverse most acute rejection episodes; however, the graft may still succumb to chronic rejection. The immunological response involved in the chronic rejection process depends on both innate and adaptive immune response. T lymphocytes have a pivotal role in chronic rejection in adaptive immune response. Meanwhile, we aim to present a general overview on the state-of-the-art knowledge of the strategies used for manipulating the lymphocyte activation mechanisms involved in allografts, with emphasis on T-lymphocyte costimulatory and coinhibitory molecules of the B7-CD28 superfamily. A deeper understanding of the structure and function of these molecules improves both the knowledge of the immune system itself and their potential action as rejection inducers or tolerance promoters. In this context, the central role played by CD28 family, especially the relationship between CD28 and CTLA-4, becomes an interesting target for the development of immune-based therapies aiming to increase the survival rate of allografts and to decrease autoimmune phenomena. Good results obtained by the recent development of abatacept and belatacept with potential clinical use aroused better expectations concerning the outcome of transplanted patients.

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MHC structure and function – antigen presentation. Part 1

Einstein (São Paulo) ◽

10.1590/s1679-45082015rb3122 ◽

2015 ◽

Vol 13 (1) ◽

pp. 153-156 ◽

Cited By ~ 10

Author(s):

Anna Carla Goldberg ◽

Luiz Vicente Rizzo

Keyword(s):

Immune Response ◽

T Cell Receptors ◽

Adaptive Immune Response ◽

Structure And Function ◽

Cell Surfaces ◽

Vast Array ◽

Innate Defense ◽

Adaptive Immune ◽

And Function ◽

Antigen Presenting

The setting for the occurrence of an immune response is that of the need to cope with a vast array of different antigens from both pathogenic and non-pathogenic sources. When the first barriers against infection and innate defense fail, adaptive immune response enters the stage for recognition of the antigens by means of extremely variable molecules, namely immunoglobulins and T-cell receptors. The latter recognize the antigen exposed on cell surfaces, in the form of peptides presented by the HLA molecule. The first part of this review details the central role played by these molecules, establishing the close connection existing between their structure and their antigen presenting function.

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Essential role of 4E-BP1 for lymphocyte activation and proliferation in the adaptive immune response of Nile tilapia

Fish and Shellfish Immunology Reports ◽

10.1016/j.fsirep.2021.100006 ◽

2021 ◽

Vol 2 ◽

pp. 100006

Author(s):

Cheng Li ◽

Kang Li ◽

Kunming Li ◽

Kete Ai ◽

Yu Zhang ◽

...

Keyword(s):

Immune Response ◽

Nile Tilapia ◽

Essential Role ◽

Adaptive Immune Response ◽

Lymphocyte Activation ◽

Adaptive Immune

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MiR-155–regulated molecular network orchestrates cell fate in the innate and adaptive immune response to Mycobacterium tuberculosis

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.1608255113 ◽

2016 ◽

Vol 113 (41) ◽

pp. E6172-E6181 ◽

Cited By ~ 52

Author(s):

Alissa C. Rothchild ◽

James R. Sissons ◽

Shahin Shafiani ◽

Christopher Plaisier ◽

Deborah Min ◽

...

Keyword(s):

Immune Response ◽

Mycobacterium Tuberculosis ◽

Cell Survival ◽

Cell Fate ◽

Adaptive Immune Response ◽

Sh2 Domain ◽

Temporal Gene Expression ◽

Adaptive Immune ◽

Adaptive Immune Cells ◽

And Function

The regulation of host–pathogen interactions during Mycobacterium tuberculosis (Mtb) infection remains unresolved. MicroRNAs (miRNAs) are important regulators of the immune system, and so we used a systems biology approach to construct an miRNA regulatory network activated in macrophages during Mtb infection. Our network comprises 77 putative miRNAs that are associated with temporal gene expression signatures in macrophages early after Mtb infection. In this study, we demonstrate a dual role for one of these regulators, miR-155. On the one hand, miR-155 maintains the survival of Mtb-infected macrophages, thereby providing a niche favoring bacterial replication; on the other hand, miR-155 promotes the survival and function of Mtb-specific T cells, enabling an effective adaptive immune response. MiR-155–induced cell survival is mediated through the SH2 domain-containing inositol 5-phosphatase 1 (SHIP1)/protein kinase B (Akt) pathway. Thus, dual regulation of the same cell survival pathway in innate and adaptive immune cells leads to vastly different outcomes with respect to bacterial containment.

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Akt1/mTORC1 signaling modulates adaptive immune response of Nile tilapia by promoting lymphocyte activation and proliferation

Developmental & Comparative Immunology ◽

10.1016/j.dci.2021.104042 ◽

2021 ◽

Vol 119 ◽

pp. 104042

Author(s):

Kete Ai ◽

Jie Yan ◽

Kang Li ◽

Cheng Li ◽

Yu Zhang ◽

...

Keyword(s):

Immune Response ◽

Nile Tilapia ◽

Adaptive Immune Response ◽

Lymphocyte Activation ◽

Adaptive Immune ◽

Mtorc1 Signaling

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Early Prognosis Effect of Cellular Immune Paralysis on Brain Complications of Extracorporeal Membrane Oxygenation Children with Severe Sepsis

NeuroImmunoModulation ◽

10.1159/000509808 ◽

2021 ◽

pp. 1-15

Author(s):

Yan Xing ◽

Dongliang Cheng ◽

Changsong Shi ◽

Zhiqing Shen

Keyword(s):

Immune Response ◽

Severe Sepsis ◽

Extracorporeal Membrane Oxygenation ◽

Adaptive Immune Response ◽

Group Iii ◽

Adaptive Immune ◽

Brain Complications ◽

Group I ◽

Group Ii ◽

The Relationship

Objective: The aim of the study was to explore the relationship between criticality, brain complications, and immune mechanisms in extracorporeal membrane oxygenation (ECMO) children with pneumonia and severe sepsis. Methods: Patients with simple pneumonia (group I), ECMO patients with pneumonia and severe sepsis accompanied by brain complications (group II), and those without brain complication (group III) admitted to our pediatric intensive care unit were selected to be investigated. The relationship among the peripheral blood subgroups of immune cells, immune factors, adaptive immune responses, endothelial factors, and criticality and brain complications was then studied. Results: Severe paralysis of normal immunity, excess abnormal immunity, and endothelial injury were consistent with the increase in the absolute value of base excess, lactic acid (Lac) content, and average hospitalization days and brain complications involved in group II (vs. group I). The ratio of CD63+ macrophage and CD63+ neutrophil subpopulation increased (p < 0.05); the expression levels of elastase+ neutrophil denatured subgroup (p < 0.05), the ratio of CCR2highCX3CR1low/CCR2lowCX3CR1high of macrophages and neutrophils (p < 0.0001), high-mobility group box 1 (HMGB1), YTHDF1, interleukin-17 protein and mRNA, and RAGE gene decreased to some extent (p < 0.05); the expression levels of Th1 cells chemokine CXCL9 protein and mRNA and sTIE2 protein increased to some extent (p < 0.05); the adaptive immune response of CD8+ CTL stimulated by lipopolysaccharide (LPS) was slightly enhanced (p < 0.05) in group III(vs. group II), which was consistent with the improvement of criticality, average hospitalization days, and the absence of brain complications in group III (vs. group II). Conclusion: ECMO support with brain complication was related to the upregulation of HMGB1 and YTHDF1 protein; the decreased number of CD63+ macrophages and neutrophils; the increased denatured neutrophil subgroup, especially the upregulated ratio of CCR2highCX3CR1low/CCR2lowCX3CR1high of macrophages and neutrophils; the imbalance of Th17/Th1, LPS-specific CD8+ CTL adaptive immune response paralysis; and the reduced endothelial sTIE2 protein expression level which caused clinical deterioration and prolonged average hospitalization days.

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Dendritic Cells as Arbiters of Peritoneal Immune Responses

Peritoneal Dialysis International ◽

10.1177/089686080602600102 ◽

2006 ◽

Vol 26 (1) ◽

pp. 8-25 ◽

Cited By ~ 6

Author(s):

Michelle L. McCully ◽

Joaquín Madrenas

Keyword(s):

Immune Response ◽

Dendritic Cells ◽

Immune Responses ◽

Adaptive Immune Response ◽

Immune Defense ◽

Dendritic Cell Differentiation ◽

Adaptive Immune ◽

The Past ◽

Key Players ◽

And Function

During the past few years, there has been a substantial increase in the understanding of innate immunity. Dendritic cells are emerging as key players in the orchestration of this early phase of immune responses, with a role that will translate into the subsequent type of adaptive immune response against infection. Here we provide an overview of dendritic cell differentiation and function, with particular emphasis on those features unique to the immune defense of the peritoneal cavity and in the context of peritoneal dialysis-associated immune responses. The reader is referred to the primary references included in the accompanying list for specific details in this fascinating field.

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