Foxp3 is regarded as the major transcription factor for T regulatory (T) cells and expression of Foxp3 is used to identify and quantitate Treg cells in mouse models. However, several studies have demonstrated that human CD4 T conventional (T) cells activated by T cell receptor (TCR) stimulation can express Foxp3. This observation has raised doubt as to the suitability of Foxp3 as a T marker in man.
View Article and Find Full Text PDFIn the midst of resurging COVID-19 cases, the second NIH/FDA virtual COVID-19 and Cytokines symposium was held on 1 December 2020, focusing on longitudinal studies of COVID-19 immunity, including long-term consequences, potential associations with autoimmunity and the multisystem inflammatory syndrome in children (MIS-C).
View Article and Find Full Text PDFCD4 Foxp3 T Regulatory (Treg) cells play a critical role in the homeostasis and maintenance of the immune system. The understanding of different aspects of Treg cells biology remains an intensively investigated subject as altering their generation, stability, or function by drugs or biologics may have therapeutic value in the treatment of autoimmune and inflammatory diseases as well as cancers. This review will focus on recent studies on the role of cytokines, T Cell Receptor (TCR) and co-stimulatory/co-inhibitory molecules signaling, location and metabolism on the homeostasis and stability of Treg cells.
View Article and Find Full Text PDFNK cells recognize MHC class I (MHC-I) Ags via stochastically expressed MHC-I-specific inhibitory receptors that prevent NK cell activation via cytoplasmic ITIM. We have identified a pan anti-MHC-I mAb that blocks NK cell inhibitory receptor binding at a site distinct from the TCR binding site. Treatment of unmanipulated mice with this mAb disrupted immune homeostasis, markedly activated NK and memory phenotype T cells, enhanced immune responses against transplanted tumors, and augmented responses to acute and chronic viral infection.
View Article and Find Full Text PDFThe production of antibody-secreting plasma cells and memory B cells requires the interaction of T follicular helper (Tfh) cells with B cells in the follicle and is modulated by T follicular regulatory (Tfr) cells. We compare the effects of Tfr cells in an model of bystander Tfh function in the absence of BCR engagement and in a model in which mimics cognate T-B interactions in which the BCR is engaged. In the absence of Tfr cells, Tfh cells from primed mice induce naive B cell differentiation into GC B cells and class switch recombination (CSR) in the presence of anti-CD3 alone or anti-CD3/IgM in a contact-dependent manner.
View Article and Find Full Text PDFBackground: Atherosclerosis is the leading cause of death worldwide. The disease development is by and large driven by old age and lifestyle factors, such as diet, physical activity, and smoking. In the present study, we have investigated the effect of exercise and diet on the development of atherosclerosis in young and aged mice.
View Article and Find Full Text PDFAtherosclerosis is the leading cause of death in the world. We have previously shown that expression of heat shock protein 60 (HSP60) on the surface of endothelial cells is the main cause of initiating the disease as it acts as a T cell auto-antigen and can be triggered by classical atherosclerosis risk factors, such as infection (e.g.
View Article and Find Full Text PDFThymoglobulin (ATG) is a polyclonal rabbit antibody against human thymocytes used as a T cell-depleting agent in organ transplantation. Its polyclonal character suggests that its effect may go far beyond just T cell depletion. The aim of this study was to further elucidate possible mechanisms underlying the suppressive activity of ATG.
View Article and Find Full Text PDFThymoglobulin (ATG) is a polyclonal rabbit antibody against human thymocytes used as a T cell-depleting agent to prevent or treat allotransplant rejection. The aim of the present study was to investigate the effect of low dose ATG treatment exclusively on T cells using a humanized BALB/c human CD3Ɛ transgenic mouse model expressing both human and murine T cell receptors (TCR). Mice received a single intravenous (i.
View Article and Find Full Text PDFObjective: The aim of this study was to identify atherogenic and atheroprotective peptides of bacterial HSP60 [taking mycobacterial HSP65 (mbHSP65) as a potent paradigmatic representative] that could be used as candidates for an orally applied tolerizing vaccine against atherosclerosis.
Methods: ApoE(-/-) mice were immunized with mbHSP65 protein or peptides, given mbHSP65 orally and then kept either on chow or high cholesterol diet. Atherosclerosis was assessed by en face and immunohistological analysis.
Atherosclerosis is a chronic, multifactorial disease that starts in youth, manifests clinically later in life, and can lead to myocardial infarction, stroke, claudication, and death. Although inflammatory processes have long been known to be involved in atherogenesis, interest in this subject has grown in the past 30-40 years. Animal experiments and human analyses of early atherosclerotic lesions have shown that the first pathogenic event in atherogenesis is the intimal infiltration of T cells at arterial branching points.
View Article and Find Full Text PDFNeutrophils are an important cellular component of the innate immune system that provides immediate protection to the host from infection. Neutrophil infiltration into inflamed peripheral tissues during infection is beneficial for immunity through phagocytosis of microbes, the release of antimicrobial factors, and secretion of proinflammatory cytokines. Recent reports further suggest that spleen-infiltrating neutrophils play a role in the adaptive immune response by providing survival signals to B cells.
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