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Granzyme B in skin inflammation and disease.

Granzyme B (GzmB) is a serine protease emerging as an important mediator of skin injury, inflammation and repair. Found at low levels in hea … ctivity in plasma, and is expressed by both immune and non-immune cells that may or may not express perforin, the pore-forming protein required for GzmB internalization into target cells. As GzmB is not normally found in the extracellular milieu, and does not appear to be regulated, GzmB-mediated proteolysis can impact processes such as tissue remodelling, …

IFNγ⁻TNFα⁻IL2⁻MIP1α⁻CD107a⁺PRF1⁺ CD8 pp65-Specific T-Cell Response Is Independently Associated With Time to Death in Elderly Humans.

Persistent cytomegalovirus (CMV) infection has been suggested to be a major driving force in the immune deterioration and an underlying sour … . Specific T-cell responses to the immunodominant antigen pp65 (IFNγ, TNFα, IL2, MIP1α, CD107a, and perforin production) were analyzed at the beginning of the 2-year observation period. A cytotoxic CD8 pp65-specific T-cell response, without cytokine or chemokine coexpression, was independently associated with all-cause mortality in these elderly individual …

The role of cytotoxic T cells in IgG4-related dacryoadenitis and sialadenitis, the so-called Mikulicz's disease.

OBJECTIVES: Immunoglobulin (Ig) G4-related dacryoadenitis and sialadenitis, the so-called Mikulicz's disease (MD), is a chronic inflammatory … s from SS patients. We performed immunofluorescence and multicolor immunofluorescence to stain CD8, perforin (PRF), granzyme B (GZMB), and PD-1. We measured the total number of CTLs as well as the PRF(+)CTLs, GZMB(+)CTLs, and PD-1(+)CTLs. RESULTS: We found that the degree of infiltration of CTLs was equal in MD and SS, but the rate of CTLs with cytotoxic …

Cytotoxic T cells mediate pathology and metastasis in cutaneous leishmaniasis.

Disease progression in response to infection can be strongly influenced by both pathogen burden and infection-induced immunopathology. While … lation and lysis of L. braziliensis infected cells. Finally, in contrast to wild-type CD8⁺ T cells, perforin-deficient cells failed to induce disease. Thus, we show for the first time that cytolytic CD8⁺ T cells mediate immunopathology and drive the development of metastatic lesions in cutaneous leishmaniasis.

Evidence for BCR-ABL-dependent dysfunctions of iNKT cells from chronic myeloid leukemia patients.

Chronic myeloid leukemia (CML) is a clonal hematopoietic stem-cell malignancy characterized by the presence of the chimeric BCR-ABL oncoprotein with deregulated tyrosine-kinase (TK) activity. Although conventional T cells are acknowledged as important players in the control of CML, a possible modification of invariant NKT (iNKT) cells, known for their antitumoral activity, has not been established as yet. Here, we showed that the expression of perforin, CD95L, and promyelocytic leukemia zinc finger, a transcription factor required for maintenance of iNKT cell functions, was reduced or suppress…

Possible role of natural killer and natural killer T-like cells in implantation failure after IVF.

During implantation, maternal immunoactivation and tolerance are not only limited to the decidua but are also observed in the periphery, pre … lations, CD69, T-cell immunoglobulin mucin 3 and NK-activating receptor expression) and functional (perforin and CD107a expression) changes in the peripheral NK and NK T (NKT)-like cell populations. During this short period of time around the IVF procedure, women with failed IVF reflected unfavourable Th1-oriented changes of NK and NKT-like cells. In compa …

Local expression of C-reactive protein is associated with deteriorating graft function in acute and chronic failure of kidney transplants.

BACKGROUND: C-reactive protein (CRP) is a key molecule in inflammation and tissue homeostasis and is produced locally by renal tubular epithelial cells. Its significance of expression in contrast to expression of cytotoxic T cell (CTL) markers remains to be elucidated. METHODS: By means of real-time PCR, we determined mRNA levels of CRP in 66 renal allograft biopsies with acute allograft failure and in 34 biopsies with chronic dysfunction. Results were compared to expression of CTL components (perforin, granzyme B) and were correlated with histologic diagnoses and outcome. RESULTS: CTL marke…

Longevity of T-cell memory following acute viral infection.

Investigation of T-cell-mediated immunity following acute viral infection represents an area of research with broad implications for both fu … course of infection. Differential regulation of the cytotoxic proteins, granzyme A, granzyme B and perforin are also observed in virus-specific T cells following infection. As a result of this work, we have gained a broader understanding of the kinetics and magnitude of antiviral T-cell immunity as well as new insight into the patterns of immunodominance …

Активирующие рецепторы поощряют расширение клеток NK для технического обслуживания, производство IL-10 и регулирование CD8 T клеток во время вирусной инфекции.

Клетки естественного убийцы (НК) способны оказывать как прямое антимикробное воздействие, так и регулировать адаптационную иммунную реакцию, однако, согласно сообщениям, урожаи клеток NK значительно различаются при различных вирусных инфекциях. Активирующие рецепторы, в том числе молекула Ly49H, признающая цитомегаловирус мыши (MCMV), могут стимулировать расширение клеток NK. Для определения роли Ly49H в поддержке распространения и обслуживания клеток NK в условиях неконтролируемой вирусной инфекции были проведены эксперименты в Ly49h(-/-), перфорине 1 (Prf1) (-/-) и мышах диких (wt) B6. Колич

Совпадение в аннотации оригинала
Natural killer (NK) cells have the potential to deliver both direct antimicrobial effects and regulate adaptive immune responses, but NK cel … tenance under conditions of uncontrolled viral infection, experiments were performed in Ly49h(-/-), perforin 1 (Prf1)(-/-), and wild-type (wt) B6 mice. NK cell numbers were similar in uninfected mice, but relative to responses in MCMV-infected wt mice, NK cell yields declined in the absence of Ly49h and increased in the absence of Prf1, with high rates of …

Stevens-Johnson syndrome and toxic epidermal necrolysis.

Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are rare, but potentially life threatening, diseases characterized by wi … nario suggested by today's literature points towards drug-specific CD8+ cytotoxic T cells utilizing perforin/granzyme B trigger keratinocyte apoptosis. Subsequently, there may be an expansion of apoptosis involving the interaction of either membrane-bound or soluble Fas ligand (sFasL) with its receptor Fas. The cellular source of sFasL remains controversia …

Biomarkers-a potential route for improved diagnosis and management of ongoing renal damage.

Currently, the identification and validation of biomarkers of kidney injury is among the top priorities of many diagnostic biotechnology com … amage include neutrophil gelatinase-associated lipocalin (NGAL), interleukin (IL)-18, soluble CD30, perforin, and granzyme B. Recently, C4d flow panel reactive antibodies were evaluated as biomarkers for humoral alloimmune responses. Additional biomarkers such as FOXP3 and kidney injury molecule 1 have been studied in the maintenance phase of renal transpl …

Function of CD8+ T lymphocytes in a self-curing mouse model of visceral leishmaniasis.

CD8+ T lymphocytes play an important role in the control of visceral leishmaniasis in non self-cure mice (e.g. BALB/c). In the present study, the mode of action of CD8+ T cells and their in vivo contribution to immunity was addressed in self-curing C57BL/6 mice. During the course of the experimental infection, CD8+ T cells specific for Leishmania infantum (L. infantum) developed and apoptotic cell death subsequently followed. They exhibited perforin-dependent cytotoxicity and a T(C)1 profile characterized by secretion of IFN-gamma and CC chemokines. Despite evidence for activation of CD8+ T ly…

Circadian oscillations of clock genes, cytolytic factors, and cytokines in rat NK cells.

A growing body of knowledge is revealing the critical role of circadian physiology in the development of specific pathological entities such … lock-controlled output gene), CREB (involved in clock signaling), cytolytic factors (granzyme B and perforin), and cytokines (IFN-gamma and TNF-alpha) in NK cells enriched from the rat spleen. The results obtained from this study demonstrate for the first time the existence of functional molecular clock mechanisms in NK cells. Moreover, the circadian expre …

NK cell activation by dendritic cells is dependent on LFA-1-mediated induction of calcium-calmodulin kinase II: inhibition by HIV-1 Tat C-terminal domain.

In this study, we show that binding to autologous dendritic cells (DC) induces a calcium influx in NK cells, followed by activation of the calcium-calmodulin kinase II (CAMKII), release of perforin and granzymes, and IFN-gamma secretion. CAMKII is induced via LFA-1: indeed, oligomerization of LFA-1 leads to CAMKII induction in NK cells. Moreover, release of lytic enzymes and cytotoxic activity is strongly reduced by masking LFA-1 or by adding CAMKII inhibitors such as KN62 and KN93, at variance with the inactive compound KN92. NK cell-mediated lysis of DC and IFN-gamma release by NK cells upon…

Understanding the immunopathogenesis of inclusion-body myositis: present and future prospects.

Sporadic Inclusion Body Myositis (s-IBM) is the most common acquired inflammatory myopathy. It has a stereotypic clinical presentation and a … minent even late in the disease, is characterized by activated, CD8+ cytotoxic T cells that secrete perforin and invade MHC-I-expressing muscle fibers. The autoinvasive T cells are probably antigen driven because of specific rearrangement of their T Cell Receptor profile, restriction of the CDR3 region, upregulation of co-stimulatory molecules and their li …

Immunoproteasomes largely replace constitutive proteasomes during an antiviral and antibacterial immune response in the liver.

The proteasome is critically involved in the production of MHC class I-restricted T cell epitopes. Proteasome activity and epitope productio … ere markedly reduced in IFN-gamma(-/-) mice, but were only slightly affected in IFN-alphaR(-/-) and perforin(-/-) mice. The proteasome regulator PA28alpha/beta was up-regulated, whereas PA28gamma was reduced in the liver of lymphocytic choriomeningitis virus-infected mice. Proteasome replacements in the liver strongly altered proteasome activity and were u …

Defective humoral responses and extensive intravascular apoptosis are associated with fatal outcome in Ebola virus-infected patients.

Ebola virus is very pathogenic in humans. It induces an acute hemorrhagic fever that leads to death in about 70% of patients. We compared the immune responses of patients who died from Ebola virus disease with those who survived during two large outbreaks in 1996 in Gabon. In survivors, early and increasing levels of IgG, directed mainly against the nucleoprotein and the 40-kDa viral protein, were followed by clearance of circulating viral antigen and activation of cytotoxic T cells, which was indicated by the upregulation of FasL, perforin, CD28 and gamma interferon mRNA in peripheral blood m…

Idiopathic giant cell myocarditis after autologous hematopoietic stem cell transplantation and interleukin-2 immunotherapy: a case report.

BACKGROUND: Interleukin-2 (IL-2) is used in the treatment of solid tumors and hematologic malignancies. Sudden death is a rare complication … ere predominantly CD4 positive T cells, and the majority of these cells stained with antibodies for perforin, suggesting an unusual cytolytic role for these lymphocytes. DNA end-labeling of myocardial tissue sections revealed numerous apoptotic myocytes within the lymphocytic infiltrate. CONCLUSIONS: To the authors' knowledge, this is the first report of …

Extracellular release by Trichomonas vaginalis of a NADP+ dependent malic enzyme involved in pathogenicity.

This report presents evidence showing that Trichomonas vaginalis releases in the extracellular environment a functional form of NADP(+)-depe … sis of the most recent findings on T. vaginalis pathogenetic mechanism, which involves pH-dependent perforins, a role for the secreted enzyme as part of the system is proposed.

Defective natural killer cell activity in B-cell chronic lymphocytic leukaemia is associated with impaired release of natural killer cytotoxic factor(s) but not of tumour necrosis factor-alpha.

The mechanisms accounting for the impaired natural killer cell activity (NKa) in B-cell chronic lymphocytic leukaemia (B-CLL) were investiga … ha by NK cells. Further studies on the production and release of other cytolytic molecules, such as perforin and granzymes, as well as studies on the possible inability of NK cells to activate the apoptotic mechanisms in the target cells are in progress in our laboratory.