Quantitative Peripheral Blood Perturbations of γδ T Cells in Human Disease and Their Clinical Implications

Human γδ T cells, which play innate and adaptive, protective as well as destructive, roles in the immune response, were discovered in 1986, but the clinical significance of alterations of the levels of these cells in the peripheral blood in human diseases has not been comprehensively reviewed. Here, we review patterns of easily measurable changes of this subset of T cells in peripheral blood from relevant publications in PubMed and their correlations with specific disease categories, specific diagnoses within disease categories, and prognostic outcomes. These collective data suggest that enumeration of γδ T cells and their subsets in the peripheral blood of patients could be a useful tool to evaluate diagnosis and prognosis in the clinical setting.     

Cross-talk between Natural Killer Cells and Dendritic Cells in Innate and Adaptive Immunity

Effective immunity requires the coordinated activation ofboth innate and adaptive immune systems. Innate immu nity is evolutionarily older than adaptive immunity, draw ing immunologists′attention again after several decades offascination with the genera…     

Stem Cells in the Treatment of Cardiovascular Disease—An Overview

CVD irreversibly damage the cardiomyocytes, the heart muscle cells. This loss triggers a cascade of detrimental events, including formation of scar tissue, an overload of blood flow and pressure capacity, the overstretching of viable cardiac cells, leading to heart failure and eventual death. Restoring damaged heart muscle tissue, through repair or regeneration, is a potentially new strategy to treat heart failure and various other CVD. Stem cells are promising new therapeutics for patients with different heart diseases. The remarkable proliferative and differentiation capacity of stem cells promises an unlimited supply of specific cell types including viable functioning heart muscle cells. A crucial issue in designing more rational cell-based therapy approaches for cardiac disease is understanding the mechanisms by which each of the stem cell or progenitor-cell types can affect myocardial performance. This paper will highlight findings of multiple preliminary clinical experiments involving stem cells as therapeutics, educate the reader on the incidence and prevalence of CVD, the risk factors associated with CVD, and explore some of the challenges that can be encountered.     

High Incidence of Morphological Myelodysplasia and Apoptotic Bone Marrow Cells in Behçet’s Disease

Beh?et's disease (BD) is a systemic inflammatory disorder of unknown etiology, and rarely complicated with myelodysplastic syndrome (MDS). In the present study, we investigated the morphological myelodysplasia and apoptotic rate of bone marrow cells in 15 patients with BD in comparison with MDS patients. Morphological myelodysplasia of bone marrow cells was detected in 53.3% of BD, but none showed chromosomal abnormalities. The apoptotic rate in BD patients (26.1 +/- 8.4%) was significantly higher in normal controls (11.3 +/- 2.4%; p < 0.005) and significantly lower in patients with MDS (50.8 +/- 14.0%; p < 0.0001). These findings suggest that myelodysplasia in patients with BD is more frequent than expected, and possibly due to excess induction of apoptosis of bone marrow cells in BD. However, the rate of apoptotic bone marrow cells is lower than MDS, which may explain the slight peripheral cytopenia in BD, distinct from that in MDS.     

Critical Role of Truncated α-Synuclein and Aggregates in Parkinson's Disease and Incidental Lewy Body Disease

The role of Lewy bodies, Lewy neurites and α-synuclein (αSYN) in the pathophysiology and diagnosis of Parkinson's disease (PD) is unclear. We used postmortem human tissue, a panel of antibodies (Abs) and confocal microscopy to examine the three-dimensional neurochemical anatomy of the nigrostriatal system. Abs were specific to truncated (tαSYN), phosphorylated and full-length αSYN. The findings demonstrate the critical role of tαSYN in initiating aggregation, a role for other forms of αSYN in aggregate expansion, a reason for the wide variety of proteins present in different aggregates, an explanation for the laminar appearance of aggregates described historically using different methods, the existence of proximal greater than distal aggregation in the vulnerable nigrostriatal pathway, the independent transport of different forms of αSYN as cargo along axons and a possible sequence for the formation of Lewy bodies. Findings differed between incidental Lewy body disease and PD only quantitatively. These findings have implications for understanding the pathogenesis and treatment of PD.     

Interferon-γ Expression in Natural Killer Cells and Natural Killer T Cells Is Suppressed in Early Pregnancy

Recent study has suggested that innate immune system might play an important role in pregnancy progression. In this study, to investigate whether NK cells and NKT cells, instead of T cells, are the dominant populations of peripheral blood in early pregnancy, flow cytometry was used to detect the percentage and intracellular cytokine expressions of T cells, NK cells, NKT cdls in peripheral blood of non-pregnant women and early pregnant women. In our result, the percentages of NK calls and NKT calls were significantly increased in pregnancy compared to non-pregnancy. However, the percentage of T cells was not changed. We did not detect the Th2-dominance of total lymphocytes or T cells in peripheral blood of early pregnant women and there were also no significant changes of type 1 and type 2 cytokines in T cells, but IFN-γ production in both NK and NKT cells was decreased in early pregnancy. These results suggest that the innate immune system including NK cells and NKT cells should play a pivotal role in pregnancy progression. Type 1/type 2 shift mechanisms in innate immune system during the human early pregnancy should be paid more attention.     

Diabetes, Renal and Cardiovascular Disease in p47 phox−/− Chronic Granulomatous Disease

Chronic granulomatous disease is a rare immunodeficiency due to defects in the phagocyte NADPH oxidase. The X-linked form (gp91 ^phox deficiency) accounts for about 70 % of cases; autosomal recessive p47 ^phox deficiency accounts for about 25 % of cases. We identified a 10 % incidence of diabetes in p47 ^phox deficient CGD, but none in X-linked CGD. Renal and cardiovascular diseases were also higher in p47 ^phox deficiency. p47 ^phox deficient CGD has non-infectious morbidities distinct from those in X-linked CGD.     

Chemokines and Chemokine Receptors： Their Manifold Roles in Homeostasis and Disease

Chemokines are a superfamily of small proteins that bind to G protein-coupled receptors on target cells and were originally discovered as mediators of directional migration of immune cells to sites of inflammation and injury. In recent years, it has become clear that the function of chemokines extends well beyond the role in leukocyte chemotaxis. They participate in organ development, angiogenesis/angiostasis, leukocyte trafficking and homing, tumorigenesis and metastasis, as well as in immune responses to microbial infection. Therefore, chemokines and their receptors are important targets for modulation of host responses in pathophysiological conditions and for therapeutic intervention of human diseases.     

Mecanotransduction and Endothelial Cells

1 IntroductionAtherosclerosis preferentially occurs in areas of complex blood flow where there are disturbed flow and low fluid shear stress, whereas laminar blood flow and high shear stress are atheroprotective~([1]). Reports of others and our studies suggest a steady laminar flow decreases some molecules and genes expression of vascular endothelial cells (EC) that may promote atherosclerosis, as well as it can differentially regulate production of many vasoactive factors at the level of gene…     

γδ T Cells in Host Defense and Epithelial Cell Biology

Recent studies have demonstrated increased numbers of γδ T cells in a variety of human infectious as well as noninfectious diseases. In some cases γδ T cells could be shown to destroy infected or transformed cells. Advances in the identification of ligands recognized by γδ T cells and the development of animal model systems to study these cellsin vivoshould overcome some of the major obstacles currently preventing a better understanding of γδ T cell function in immune responses. As we gain this knowledge it may become possible to design therapeutic strategies exploiting unique properties of γδ T cells to promote more effective immunity.     

Stem Cells in Tooth Tissue Regeneration—Challenges and Limitations

The accelerated pace of research in the stem cell field in recent decades and the accumulated body of knowledge has spurred the interest in potential clinical applications of stem cells in all branches of medicine including regenerative dentistry. In humans, embryonic and adult stem cells are two major groups of cells that can serve as a donor source in tissue engineering strategies based on ex-vivo cellular expansion. It has been shown that adult stem cell populations are present in all examined living tissues of the organism, thus being a crucial source of tissue homeostasis and regeneration, and offering a target population for in situ stimulation of extensive tissue regeneration. Experimental findings indicate that in the complex structure of the tooth organ, both periodontal and endodontic tissues harbour adult stem cells with characteristics peculiar to early stages of cellular differentiation. Myriad of strategies incorporating both embryonic and adult stem cells for the regeneration of a particular tooth structure or the whole teeth were proposed; however their successful application to solve real problems encountered in the clinical practice of dentistry remains an elusive and challenging objective.     

Phenotypic Heterogeneity in Cell Proliferation and Radiosensitivity in Human Laryngocarcinoma Hep-2 Cells

1 IntroductionRadiotherapy is one of the major clinical treatments for malignant tumors. However, tumor cells are heterogenic in response to radiation (radiosensitivity) which limits the achievement ratio of radiotherapy in many non-sensitive tumors. At the same time, radiosensitivity plays an important role in radiobiology and it is regarded as the fifth “R”- Radiosensitivity in fractionation radiotherapy. Understanding the mechanism of heterogeneity of tumor cell radiosensitivity is criti…     

Natural Killer Cells： Biology and Clinical Use in Cancer Therapy

Natural killer (NK) cells have the ability to mediate both bone marrow rejection and promote engraftment,aswell as the ability to elicit potent anti-tumor effects.However the clinical results for these processes are stillelusive.Greater understanding of NK cell biology,from activating and inhibitory receptor functions to the roleof NK cells in allogeneic transplantation,needs to be appreciated in order to draw out the clinical potential ofNK cells.Mechanisms of bone marrow cell (BMC) rejection are known to be dependant on inhibitory receptorsspecific for major histocompatibility complex (MHC) molecules and on activating receptors that have manypotential ligands.The modulation of activating and inhibitory receptors may hold the key to clinical successinvolving NK cells.Pre-clinical studies in mice have shown that different combinations of activating andinhibitory receptors on NK cells can reduce graft-versus-host disease (GVHD),promote engraftment,andprovide superior graft-versus-tumor (GVT) responses.Recent clinical data have shown that the use ofKIR-ligand incompatibility produces tremendous graft-versus-leukemia effect in patients with acute myeloidleukemia at high risk of relapse.This review will attempt to be a synthesis of current knowledge concerning NKcells,their involvement in BMT,and their use as an immunotherapy for cancer and other hematologicmalignancies.Cellular & Molecular Immunology.2004;1(1):12-21.