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Large granular lymphocyte leukaemias (LGL) are rare lymphoproliferative syndromes characterised by clonal expansion of T or NK lymphocytes in 85 and 15% of cases respectively. Interestingly, T and NK LGL leukaemias share a common pathophysiology and similar clinical and biological presentations. This lymphoproliferative syndrome is characterised by cytopenias and a frequent association with autoimmune diseases or manifestations. It is an indolent disease that in most cases allows for an abstinence-only strategy at diagnosis. However, the majority of patients will require initiation of treatment during follow-up. As NK cells lack a TCR, obtaining evidence of clonality in NK-ALL leukaemias is difficult. This is crucial in view of possible reactive expansions in the context of viral infections or dysimmune diseases. The diagnostic approach has been facilitated by the progress made in recent years in the understanding of the pathophysiology and the recent identification of recurrent mutations. In this review, we will discuss the pathophysiology of NK LGL leukaemias, present recent advances in diagnostic strategies before discussing therapeutic management. [ABSTRACT FROM AUTHOR]

Untreated HIV infection usually leads to disease progression and development of the acquired immunodeficiency syndrome. A rare subset of people living with HIV control HIV without anti-retroviral therapy. These individuals, known as Elite Controllers (ECs), represent examples of a functional HIV cure. ECs differ from non-controllers is many aspects. Some are infected with defective virus, most have potent CD4 and CD8 virus-specific T cell responses and proviruses in these individuals tend to be inserted into regions with characteristics of deep latency. Natural Killer (NK) cells are innate immune cells that function at the intersection of innate and adaptive immunity. They have the capacity to recognize and respond to HIV-infected cells from the earliest stages in infection. NK cells can be activated through antibody independent and antibody dependent mechanisms to elicit functions that control HIV and kill infected cells. This manuscript will review the role of NK cells in HIV control. [ABSTRACT FROM AUTHOR]

Untreated HIV infection usually leads to disease progression and development of the acquired immunodeficiency syndrome. A rare subset of people living with HIV control HIV without anti-retroviral therapy. These individuals, known as Elite Controllers (ECs), represent examples of a functional HIV cure. ECs differ from non-controllers is many aspects. Some are infected with defective virus, most have potent CD4 and CD8 virus-specific T cell responses and proviruses in these individuals tend to be inserted into regions with characteristics of deep latency. Natural Killer (NK) cells are innate immune cells that function at the intersection of innate and adaptive immunity. They have the capacity to recognize and respond to HIV-infected cells from the earliest stages in infection. NK cells can be activated through antibody independent and antibody dependent mechanisms to elicit functions that control HIV and kill infected cells. This manuscript will review the role of NK cells in HIV control. [ABSTRACT FROM AUTHOR]

Immunotherapy for digestive cancers is booming and for the first time an immune checkpoint inhibitor has been granted marketing authorization for the treatment of digestive cancer. In order to better understand the mecanism of action of these treatments, their adverse events and the escape mecansim, it is necessary to know the fundamentals of cancer immunology. The innate and adaptive immune system allows the elimination of cancer cells by direct non-specific cytotoxicity (Natural Killer cells), by the development of an adaptive cell-mediated response (dendritic cells becoming antigen presenting cells, allowing the differentiation of lymphocytes naive in CD4 and CD8 T lymphocytes) and by humoral immunity (via B lymphocytes). A state of equilibrium can be established. One of the oncogenesis processes is then the escape of tumor cells from immune control, by the loss of their antigen presentation capacity, by the recruitment of immunosuppressive cells or by the expression on their surface of inhibitory costimulatory molecules (PD-L1, Galectin 9) interacting with their ligand on the lymphocyte (PD-1, Tim-3) and resulting in inactivation of the immune response. These proteins correspond to immune checkpoints and are the target of major immunotherapy molecules currently in use. A panorama of knowledge on the prognostic value of the tumor microenvironment of gastric cancers and hepatocarcinomas is then made. [ABSTRACT FROM AUTHOR]

The article focuses on the effectiveness of antiviral immunotherapy for COVID-19 pandemic. It mentions that a better understanding of immune system response facing this virus is essential for the development of therapeutics efficient. It also mentions that cells natural killer (NK) kill infected cells with mechanisms of degranulation, apoptosis mediated by receptor and dependent cell cytotoxicity mediated antibodies.

Aggressive natural killer cell leukemia (ANKL) is a disease entity within the spectrum of lymphoproliferative syndromes of NK cells. It is rare, preferentially affecting Asiatic people. It has been very rarely reported in the African population; hence the interest of our case. Our study involved a 19-year old female patient of Moroccan origin presenting with acute-onset bone marrow failure syndrome associated with tumor syndrome. The diagnosis of natural killer cell leukemia was retained based on microscopic and immunophenotypic study of the bone marrow. Patient's outcome was fatal; she died within 2 months of diagnosis due to septic shock. Patients with ANKL have a worse prognosis and the median survival time following diagnosis is, on average, two months. In the absence of a prospective study, no therapeutic guidelines have been developed. [ABSTRACT FROM AUTHOR]

Résumé: Les lymphomes NK/T sont rares en Europe et aux États-Unis mais relativement fréquents en Asie et en Amérique du Sud. Ils se présentent cliniquement comme des lésions destructrices des voies aérodigestives supérieures, préférentiellement localisées au niveau des fosses nasales, avec une atteinte possible des structures avoisinantes. Le diagnostic positif repose sur une analyse histologique, immunophénotypique et la mise en évidence du virus d’Eptein-Barr. Les modalités de traitement de ces lymphomes restent encore discutées de part le peu d’études dont nous disposons et la rareté de cette pathologie. La radiothérapie permet d’obtenir un contrôle rapide de la maladie et se place comme un traitement majeur des lymphomes NK/T localisés des fosses nasales. Elle délivre une dose 50Gy dans de larges volumes en association à une chimiothérapie à base de l-asparaginase. Nous présentons donc la place de la radiothérapie dans les formes localisées de lymphome NK/T des fosses nasales. [ABSTRACT FROM AUTHOR]

Résumé: Les leucémies à grands lymphocytes granuleux (LGL) désignent des hémopathies caractérisées par la prolifération monoclonale de grands lymphocytes riches en granulations azurophiles, de phénotype T CD3+CD57+ ou Natural Killer (NK) CD3–CD56+. La classification de l’Organisation mondiale de la santé (OMS) distingue ainsi trois entités : les leucémies LGLT, les expansions chroniques à cellules NK et les leucémies agressives à cellules NK. Les leucémies LGLT et les expansions chroniques à cellules NK ont une évolution indolente, principalement marquée par l’existence d’une cytopénie ou d’une pathologie auto-immune associée. Leur pronostic est conditionné par l’existence de complications infectieuses secondaires à la neutropénie. Le traitement repose en première intention sur les immunosuppresseurs (méthotrexate, ciclosporine, cyclophosphamide). Les leucémies agressives à cellules NK se présentent sous la forme d’un syndrome tumoral qui fait rapidement suspecter l’hémopathie sous-jacente. Il s’agit d’hémopathies peu chimiosensibles dont le pronostic est réservé. Les progrès récents dans la connaissance de la physiopathologie de ces hémopathies ont permis de préciser les mécanismes à l’origine de la pérennisation du clone LGL et d’identifier de nouvelles cibles thérapeutiques. [ABSTRACT FROM AUTHOR]

Résumé: La granulomatose lymphomatoïde, décrite par Liebow en 1972, est un syndrome lymphoprolifératif rare lié à l’Epstein-Barr virus (EBV) atteignant de manière prédominante le poumon et souvent la peau ou le système nerveux central. Sa présentation, volontiers systémique, en fait une maladie de diagnostic difficile. Malgré des controverses, la granulomatose lymphomatoïde est considérée comme un lymphome B dont la sévérité s’étend d’un lymphome de bas grade à un lymphome agressif de type grandes cellules. L’histologie est indispensable et montre typiquement un infiltrat inflammatoire angiocentrique, composé d’éléments mononucléés polymorphes contenant un nombre variable de grands lymphocytes B CD20+ atypiques au sein de très nombreux petits lymphocytes T CD3+ réactionnels et pouvant s’associer à de la nécrose. L’hybridation in situ permet souvent de mettre en évidence l’ARN de l’EBV au sein des cellules B atypiques. La proportion de grands lymphocytes B atypiques et, à moindre degré, la proportion de cellules EBV+ permettent de classer la maladie (grade I à III) et d’en déterminer le pronostic. La maladie peut évoluer vers une forme agressive de lymphome B, survenant dans 7 à 47 % des cas. Par ailleurs, les granulomatoses lymphomatoïdes de grade III partagent les caractéristiques d’un lymphome et doivent être traitées par polychimiothérapie. De nombreuses pathologies peuvent mimer la granulomatose lymphomatoïde, en particulier certaines hémopathies (lymphomes B à grandes cellules, lymphomes T/NK, syndromes lymphoprolifératifs post-immunodépression) ou la granulomatose avec polyangéite. L’objectif de cette revue est de rappeler les caractéristiques cliniques, radiologiques, histologiques et thérapeutiques de cette maladie. [ABSTRACT FROM AUTHOR]

Abstract: Surgical treatment of cancer is usually necessary but it can paradoxically aggravate the patient outcome by increasing the risk of recurrence. Many perioperative factors have been shown to contribute to the dissemination of the tumor: surgery itself, stress, inflammation, pain, anaesthetic drugs, blood transfusion, etc. The type of anaesthesia chosen in the cancer patient could then be crucial and influence the evolution of the disease. Experimental, preclinical and retrospective studies have suggested that a regional anesthesia associated or not with a general anesthesia for carcinologic surgery might reduce the risk of cancer recurrence. This text reviews the factors promoting the recurrence of tumors after carcinologic surgery and the potential possibilities of protection associated with the type of anaesthesia chosen. [Copyright &y& Elsevier]

Abstract: Objective: The Natural Killer cells (NK) are an important part of non-specific cellular-mediated and antitumoral immunity. The goal of this review is to recapitulate data published over NK activity during the perioperative period and the influence of anaesthesia, analgesia and modulation of sympathetic system. Data sources: Pubmed/Medline database. Study selection and data extraction: Keywords-based selection, without limit of date: fundamental studies, randomized controlled trials and non-randomized comparative studies. Data synthesis: In human as in animal studies, an important correlation exists between NK activity and prognosis linked to the development of metastasis. The great depression of this cytotoxicity during the perioperative period could be able to compromise host defenses. The influence of anaesthetics and analgesics is important. The effects of the opioids, the agonists and the antagonists of the sympathetic nervous system, the prostaglandins, the NSAIDs, the ketamine, the hypnotics and the locoregional anaesthesia are systematically reviewed. The limits of experimental model presented are covered. Conclusion: The effects of anaesthetic/analgesic drugs and techniques, the consequences of sympathomodulation on NK activity are numerous and sometimes opposite. It is important for the anaesthesiologist to keep in mind that the long term consequences of his techniques on the patients’ outcome must be clarified. [Copyright &y& Elsevier]

Abstract: The neurotransmitter 5-hydroxytryptamine (5-HT), commonly known as serotonin, is released at peripheral sites from activated platelets. At inflammatory sites, macrophages and lymphocytes could be exposed to 5-HT concentrations up to 100 μM. Moreover, 5-HT could modulate cytokine secretion by monocytes/macrophages and immune functions through the uptake of 5-HT at these inflammatory sites from T cells and dendritic cells. HIV infection is also under the control of inflammatory processes (including T cell proliferation and cytokines secretion). On this basis, we studied explored herein the effects of 5-HT on HIV-1/Ba-L (macrophage-tropic virus) replication in primary cultures of human macrophages. This pharmacological study with isotype-selective receptor agonists and antagonist allowed us to show that the 100 μM 5-HT concentration via 5-HT1A subtype receptors could decrease HIV replication. This observation was associated with an increase of MIP-1α secretion such as an increase of MIP-1α mRNA production and with a decrease of HIV-coreceptor CCR5 cell surface expression. Our results point out for the first time the inhibitory effects of 5-HT on HIV replication in primary culture of human macrophages via activation of 5-HT1A subtype receptors. [Copyright &y& Elsevier]

Abstract: Introduction. – Natural killer cells are cytotoxic lymphocytes of innate immunity. These last ten years our knowledge about the mechanisms that regulates NK cell function has greatly improved. Our purpose is to present a review of these new acquisitions and their potential implications in human disease. Current knowledge and key points. – NK cell function is regulated by a repertoire of NK cell receptors and is diversified by recognition of MHC class I by a multigenic and mutiallelic family of NK receptors. Analysis of NK cell repertoire has been used to investigate features that characterize NK cells in pathological situations. Apart from their direct cytotoxic potential to eliminate target cells, recently identification of mechanisms that control NK cell mediated cytokine production and cross talk with dendritic cells emphasize the role of NK cells in the regulation of acquired immune response. Future prospects and projects. – These findings have lead to a better knowledge of the importance of the NK cells in several human diseases. It has been shown that NK cells are actors of the immunosurveillance of tumoral and infectious challenges. Allo or auto reactivity of the NK cell compartment have also been suggested in autoimmune diseases, infertility or foetal loss and transplantation. Ongoing research on NK cells in the fields of human diseases is increasing and will clarify the utility of the evaluation of the NK cell compartment and their receptors in clinical practice. [Copyright &y& Elsevier]

Abstract: Background. – Systematic plasma leukoreduction, which was introduced in France in April 1st 2001, has given rise to more sensitive methods for residual leukocytes counting. The technologies in application at this moment (Nageotte hemocytometers and flow cytometry methods) have been modified by a thirty fold sample concentration prior to analysis, inducing frequent downgrading of the plasma unit. So, in order to improve the detection threshold, we developed a more sensitive assay using “Real-Time Polymerase Chain Reaction” technology. Materials and methods. – Real-time polymerase chain reaction was performed on a highly conserved HLADQα1 gene sequence. In order to determine the analytical performances of the method (accuracy, sensitivity, linearity and specificity) serial dilutions series ranging from 104 to 1 cells/ml were performed. A total of 18 series were prepared from three leukocyte stock solutions, by 1 in 10 serial dilutions in three plasmas completely devoided of white cells (called negative plasmas). To examine the specificity of the assay two negative controls were analyzed in each run. Results. – a sensitivity of 10 cells/ml (104 leukocytes/l) was achieved and the assay was linear between 10 and 104 cells/ml. The slope (–3.72) of the average standard curve calculated from all series, showed an amplification yield of 92.85%. Conclusion. – we developed a quantitative assay for residual leukocytes in leukodepleted plasma, that agreed with the quality control requirement specifications. [Copyright &y& Elsevier]

Abstract: Calcium phosphate bioceramics have been applied as bone substitutes for several decades. Aseptic loosening after total joint arthroplasty is a major problem in orthopaedic surgery. Hydroxyapatite particles from materials wear have been reported as the main cause of implant failure. For this reason, an investigation into possible wear particles from materials used in the implant may lead to increase the longevity of implants after arthroplasty. In the present paper, we discussed the cellular response (mainly monocytes/macrophages which are among the first cells to colonize the inflammatory site in addition to osteoblats and fibroblasts) after exposition to particles with different characteristics (size, sintering temperature, shape, and chemical composition). The most important characteristics are the shape and the size of the particles. The needle shaped particles induced the larger production of inflammatory mediators by cells and were more toxic. The sintering temperature appeared to be a less important characteristic even though it was involved in the dissolution/precipitation process. Little is known about the effect of ion containing hydroxyapatite (like zinc, strontium, …) on cellular response but this modification of the biomaterial seems benefic. [Copyright &y& Elsevier]

IgE is produced mainly by plasma cells in diffuse mucosal-associated lymphoid tissues. Its synthesis is the result of three sets of tightly-regulated processes: activation of antigen-specific B cells in lymph nodes, class-switch recombination to IgE and survival of Bϵ memory cells and plasma cells. Triggered by specific T lymphocytes that have migrated to regional lymph nodes, the switch to IgE within follicular areas of these nodes is driven by the interaction of the CD40 receptor with its ligand on activated T cells, acting together with IL-4 and IL-13, whereas TGF-β specifically blocks Cϵ germline transcription to keep the rate of IgE synthesis far lower than that of other immunoglobulin classes. Disproportionate maturation of dendritic cells exposed to non-replicating environmental antigens, promoting the differentiation of specific T cells into effectors that produce type 2 cytokines instead of inducing regulatory T cells, is essential for the initiation and maintenance of IgE responses beyond the sensitization phase. Feedback regulation via IgE receptors (e.g., FcϵRI) and inflammatory mediators compartmentalizes IgE synthesis in the mucosa by orchestrating the cooperation of dendritic cells, memory lymphocytes, and mast cells. [Copyright &y& Elsevier]

Function of T and natural killer (NK) lymphocytes is tightly controlled by the balance of activating and inhibitory signals. NK receptors belong to different families: KIRs (“Killer cell Immunoglobulin-like Receptor”) and ILTs (“Immunoglobulin-like Transcript”), mainly inhibitory which binds to HLA class I alleles; C-type lectin NK receptors such as CD94/NKG2A which is inhibitory and binds to HLA-E ; NCR (“Natural Cytotoxicity Receptors”) which directly activate NK cells. These include molecules NKp30, NKp44, NKp46 et NKG2D. Cellular stress (viral and bacterial infections, tumours) may modulate NK function by different mechanisms: decrease in HLA class I molecules expression resulting in the lack of engagement of the inhibitory receptors and ultimately NK cell activation; modulation of CD94/NKG2A inhibitory function through expression of peptides presented by HLA-E as for instance from heat shock proteins; NK activation through NCR expression. Among these, NKG2D is an activating receptor expressed by NK cells and subsets of αβ and γδ and T cells. Major NKG2D ligands in humans are MIC (“MHC class I related”) molecules which are stress-inducible during a viral (CMV) or bacterial infection (M. tuberculosis, E. coli). They may also be expressed by tumors. Therefore, they could play a role in activating NK and/or T lymphocyte responses in these conditions. [Copyright &y& Elsevier]

Abstract: Objective: The authors had for aim to determine the role of leukoconcentration in the diagnosis of visceral leishmaniosis in immunocompetent children. Materials and methods: A study was made on leukoconcentration in blood samples of 84 immunocompetent children presenting with visceral leishmaniosis, hospitalised in the paediatric units of Sousse and Kairouan (Tunisian center) between April 1996 and March 2005. Results: The study group included 34 girls and 50 boys (sex-ratio=1.47) aged six months to ten years. In this group, 47 patients (56%) presented with positive leukoconcentration. The number of leishmania detected ranged from 1 to 64 per slide; parasitism of PMN leucocytes was noted in nearly half of the cases. Conclusion: Parasitemia is frequent in the Mediterranean Kala-azar; therefore leukoconcentration on peripheral blood can be proposed as a first intention examination for the diagnosis of visceral leishmaniosis in immunocompetent children. [Copyright &y& Elsevier]

Les greffeurs ont de nouveau recours aux greffes haplo-identiques de cellules souches hématopoïétiques (CSH), sans déplétion des lymphocytes T, grâce au traitement post-greffe basé sur l'administration de forte dose d'un immunosuppresseur, le cyclophosphamide. Pour ces couples donneur/receveur (D/R), le nombre d'incompatibilités (inc.) HLA entre le D et le R est important et peut impacter les réponses cellulaires Natural Killer (NK) KIR et le pronostic clinique du patient. Dans cette étude rétrospective, nous avons étudié l'impact des inc. génétiques KIR/HLA sur le devenir des patients en lien avec les résultats cliniques et la reconstitution des cellules NK dans une cohorte de 51 patients. La reconstitution du répertoire cellulaire NK a été étudiée par cytométrie de flux chez 34 de ces 51 patients de J0 à J100 après la greffe. Les inc. impliquant les KIR2DL ont été significativement associées à la maladie du greffon contre l'hôte, GvHD (81,2 % vs 45,7 %, p = 0,01) et à moins de rechute (6,2 % vs 42,8 %, p = 0,008). Le profil phénotypique des cellules NK a été significativement différent chez les patients avec rechute et ceux qui développent une GvHD. En effet, les patients associés à des inc. KIR/HLA développent plus de GvHD et présentent précocement des cellules NK différenciées qui arrivent plus tardivement chez les patients en rechute. Parce que plusieurs donneurs haplo-identiques peuvent être identifiés dans une famille, la prédiction de l'alloréactivité des cellules NK KIR basée sur les inc. KIR/HLA pourrait être utile pour la sélection des donneurs pour optimiser le devenir des patients. [ABSTRACT FROM AUTHOR]