ABSTRACT
The large majority of lymphocytes belong to the adaptive immune system, which are made up of B2 B cells and the αß T cells; these are the effectors in an adaptive immune response. A multitudinous group of lymphoid lineage cells does not fit the conventional lymphocyte paradigm; it is the unconventional lymphocytes. Unconventional lymphocytes-here called innate/innate-like lymphocytes, include those that express rearranged antigen receptor genes and those that do not. Even though the innate/innate-like lymphocytes express rearranged, adaptive antigen-specific receptors, they behave like innate immune cells, which allows them to integrate sensory signals from the innate immune system and relay that umwelt to downstream innate and adaptive effector responses. Here, we review natural killer T cells and mucosal-associated invariant T cells-two prototypic innate-like T lymphocytes, which sense their local environment and relay that umwelt to downstream innate and adaptive effector cells to actuate an appropriate host response that confers immunity to infectious agents.
Subject(s)
Mucosal-Associated Invariant T Cells , Natural Killer T-Cells , Immunity, Innate , Lymphocytes , Adaptive ImmunityABSTRACT
Currently, as the SARS-CoV-2 pandemic evolves, there has been increasingly more attention paid to building natural and vaccine-induced immunity against SARS-CoV-2 and related disease known as COVID-19. Widespread preventive vaccination plays an important role in effectively protecting people from viral infections and can reduce national economic costs. Purpose - to study peripheral blood cell subset composition and magnitude of humoral response in vaccinated Gam-COVID-Vac subjects. The prospective study included 352 patients, of which 194 (119 women and 75 men) underwent an immunogram study and assessed level of anti-SARS-CoV-2 antibodies. In patients, the study of the lymphocyte subset composition and estimation of anti-SARS-CoV-2 antibodies was carried out at two time points - prior to vaccination and 90 days after inoculated component 1 of the Gam-COVID-Vac vaccine. In general, vaccination was well tolerated by patients, with no serious adverse events after immunization. The reaction to the vaccine (fever, malaise, headache, local reactions) was short-term (1-2 days) and more often noted after inoculated vaccine component 2. Comparatively analyzed immunogram parameters in females before and after vaccination revealed increased relative level of T-lymphocytes (CD3+), T-helper cell subset (CD3+CD4+), increased absolute and relative level of activated CD3+CD25+ T-lymphocytes, but decreased absolute and relative level of natural killer (CD3-CD56+CD16+) and natural killer T-cell (CD3+CD56+CD16+) cell subsets as well as decreased CD147 receptor expression on T-lymphocytes. Similar patterns were also found while examining the immunogram in males exepting increased level of lymphocytes and lowered CD147 expression on both T- and B-lymphocytes. No changes in the parameters of the immune T-cell arm was found. The high efficacy of the vaccine was confirmed by development of SARS-CoV-2-specific class G antiviral antibodies in 97.5% and 92.3% of vaccinated females and males, respectively. The data obtained evidence that: 1) vaccination induces a specific humoral immune response determined three months post-vaccination, and 2) it caused no serious disturbances in the immune system functioning, which could be reflected in the peripheral blood lymphocyte subset composition. Thus, the data presented allow to conclude that Gam-COVID-Vac is effective vaccine against SARS-CoV-2 infection.Copyright © 2022 Saint Petersburg Pasteur Institute. All rights reserved.
ABSTRACT
Malignant pulmonary lymphoma is very rare and the majority of which are B-cell lymphomas. Since primary pulmonary extranodal natural killer (NK)/T-cell lymphoma, nasal type (ENKL) is difficult to diagnose and associated with poor prognosis and aggressive course, some cases are diagnosed at the postmortem autopsy. We report a case of a 53-year-old man with primary pulmonary ENKL diagnosed by video-assisted thoracoscopic surgery (VATS) lung biopsy. This case explains the importance of VATS lung biopsy and in-depth evaluation, including flow cytometry, chromosome, genetic, and immunostaining tests, when primary pulmonary malignant lymphoma is suspected.
ABSTRACT
Currently, as the SARS-CoV-2 pandemic evolves, there has been increasingly more attention paid to building natural and vaccine-induced immunity against SARS-CoV-2 and related disease known as COVID-19. Widespread preventive vaccination plays an important role in effectively protecting people from viral infections and can reduce national economic costs. Purpose - to study peripheral blood cell subset composition and magnitude of humoral response in vaccinated Gam-COVID-Vac subjects. The prospective study included 352 patients, of which 194 (119 women and 75 men) underwent an immunogram study and assessed level of anti-SARS-CoV-2 antibodies. In patients, the study of the lymphocyte subset composition and estimation of anti-SARS-CoV-2 antibodies was carried out at two time points - prior to vaccination and 90 days after inoculated component 1 of the Gam-COVID-Vac vaccine. In general, vaccination was well tolerated by patients, with no serious adverse events after immunization. The reaction to the vaccine (fever, malaise, headache, local reactions) was short-term (1-2 days) and more often noted after inoculated vaccine component 2. Comparatively analyzed immunogram parameters in females before and after vaccination revealed increased relative level of T-lymphocytes (CD3+), T-helper cell subset (CD3+CD4+), increased absolute and relative level of activated CD3+CD25+ T-lymphocytes, but decreased absolute and relative level of natural killer (CD3-CD56+CD16+) and natural killer T-cell (CD3+CD56+CD16+) cell subsets as well as decreased CD147 receptor expression on T-lymphocytes. Similar patterns were also found while examining the immunogram in males exepting increased level of lymphocytes and lowered CD147 expression on both T- and B-lymphocytes. No changes in the parameters of the immune T-cell arm was found. The high efficacy of the vaccine was confirmed by development of SARS-CoV-2-specific class G antiviral antibodies in 97.5% and 92.3% of vaccinated females and males, respectively. The data obtained evidence that: 1) vaccination induces a specific humoral immune response determined three months post-vaccination, and 2) it caused no serious disturbances in the immune system functioning, which could be reflected in the peripheral blood lymphocyte subset composition. Thus, the data presented allow to conclude that Gam-COVID-Vac is effective vaccine against SARS-CoV-2 infection.
ABSTRACT
Currently, as the SARS-CoV-2 pandemic evolves, there has been increasingly more attention paid to building natural and vaccine-induced immunity against SARS-CoV-2 and related disease known as COVID-19. Widespread preventive vaccination plays an important role in effectively protecting people from viral infections and can reduce national economic costs. Purpose - to study peripheral blood cell subset composition and magnitude of humoral response in vaccinated Gam-COVID-Vac subjects. The prospective study included 352 patients, of which 194 (119 women and 75 men) underwent an immunogram study and assessed level of anti-SARS-CoV-2 antibodies. In patients, the study of the lymphocyte subset composition and estimation of anti-SARS-CoV-2 antibodies was carried out at two time points - prior to vaccination and 90 days after inoculated component 1 of the Gam-COVID-Vac vaccine. In general, vaccination was well tolerated by patients, with no serious adverse events after immunization. The reaction to the vaccine (fever, malaise, headache, local reactions) was short-term (1-2 days) and more often noted after inoculated vaccine component 2. Comparatively analyzed immunogram parameters in females before and after vaccination revealed increased relative level of T-lymphocytes (CD3+), T-helper cell subset (CD3+CD4+), increased absolute and relative level of activated CD3+CD25+ T-lymphocytes, but decreased absolute and relative level of natural killer (CD3-CD56+CD16+) and natural killer T-cell (CD3+CD56+CD16+) cell subsets as well as decreased CD147 receptor expression on T-lymphocytes. Similar patterns were also found while examining the immunogram in males exepting increased level of lymphocytes and lowered CD147 expression on both T- and B-lymphocytes. No changes in the parameters of the immune T-cell arm was found. The high efficacy of the vaccine was confirmed by development of SARS-CoV-2-specific class G antiviral antibodies in 97.5% and 92.3% of vaccinated females and males, respectively. The data obtained evidence that: 1) vaccination induces a specific humoral immune response determined three months post-vaccination, and 2) it caused no serious disturbances in the immune system functioning, which could be reflected in the peripheral blood lymphocyte subset composition. Thus, the data presented allow to conclude that Gam-COVID-Vac is effective vaccine against SARS-CoV-2 infection. Copyright © 2022 Saint Petersburg Pasteur Institute. All rights reserved.
ABSTRACT
Objective. To clarify the features of the defect in the function of NK cells, T lymphocytes, the interferon system in patients with moderate and severe COVID-19. Patients and methods. Tests of the peripheral blood of 50 COVID-19 patients aged 61(57–71) and having the moderate and severe disease were performed. The following parameters were measured: the quantity of CD3+CD19–, CD3+CD4+, CD3+CD8+ T lymphocytes, NK – (CD3–CD16+CD56+), and TNK – CD3+CD16+CD56+ with expression density considered membrane receptors (MFI) (FC 500 Beckman Coulter, USA), the levels of IFN-α, IFN-γ, IL-6, TNF-α cytokines (IFA). Results. Combined immunodeficiency associated with quantitative and functional defects in NK, T lymphocytes and their subsets was revealed in moderate and severe COVID-19. An imbalance of cytokines has been established: blockade of the production of IFN-α and IFN-γ against the background of a significant increase in IL-6 and TNF-α, which negatively affects both the number and functionality of the participants in the immune response and is associated with a severe course and poor prognosis of COVID-19. Conclusion. The data obtained demonstrate the need to develop new strategies and tactics for the treatment of COVID-19, including replacement systemic therapy with recombinant IFN-α2b in combination with antioxidants (Viferon®) in adequate therapeutic doses, aimed at restoring the normal functioning of T lymphocytes, NK and the interferon system.
ABSTRACT
Background: Besides the ability to induce antigen-specifc responses, vaccines can be endowed with immunomodulatory properties including the capacity to induce or downregulate regulatory T cells (Treg) that suppress adaptative and autoreactive immune responses (1). Objectives: We asked if an anti-SARS-CoV-2 mRNA vaccine could also induce an accumulation of Treg cells in patients with mixed cryoglobulinemia vasculitis (MCV), who have a defciency of Treg cells (2) and in healthy individuals. We also investigated immunologic variables possibly associated with a low immunogenic-ity of SARS-CoV-2 mRNA vaccine in patients with MCV (3). Methods: We analyzed peripheral blood lymphocyte subpopulations and anti-SARS-CoV-2 serological response in 24 patients with MCV and 9 Healthy donors (HD) before and after 2 weeks after the second dose of the Pfzer/BioNTech vaccine. Results: Among MCV patients we found 15 serological responders and 9 non-responders. All 5 seronegative patients treated recently with rituximab had <5 B cells/μ L, whereas the absolute B cell count was increased in 2 of 4 untreated patients due to monoclonal B cell lymphocytosis, with monoclonal cells representing more than 90% of B cells, associated with non-Hodgkin lymphoma. The percentage of pathologic CD21low B cells was signifcantly increased in seronegative patients. Before receiving the Pfzer/BioNTech vaccine, patients with MCV had a signifcantly reduced frequency of Treg cells among CD4+ T cells compared to HD. After the second dose of the vaccine, there was in MCV patients a signifcant increase in the percent and absolute count of Treg among CD4+ T cells Concerning the pre-vaccination distribution of T cells subpopulations, including the percentages and absolute counts of total CD3+, CD4+, CD8+, HLA-DR+ activated, Treg or CD56+ natural killer T cells, we could not reveal any pattern signifcantly associated with lack of serological response to vaccine. Conclusion: Our fndings show that lack of immunoreactivity in patients with MCV may be associated with expansion of pathologic B cells and that anti-SARS-CoV2 mRNA vaccine may induce an increase of Treg cells.
ABSTRACT
Dexamethasone has been widely used since its initial approval by the FDA in 1958, either individually or as part of a therapeutic regimen for a variety of diseases and disorders, including lymphoma and leukemia and most recently, COVID-19 mediated disease. During a preclinical experiment with A20 B-cell lymphoma bearing mice, a suprapharmacologic dose of dexamethasone phosphate, equivalent to a Human (Equivalent) Dose of 17.5 mg/kg, was inadvertently administered. Blood samples were collected and analyzed by flow cytometry, revealing the presence of a new cell 48 hours after dosing. Subsequent experiments confirmed this finding following a single dose of AVM0703. This cell has since been identified as a bi-specific gamma-delta+ NKT cell, or AVM-NKT cell. One of the challenges of being able to deliver suprapharmacologic dexamethasone doses was the drug product itself. These limitations led to the development of a new drug product, AVM0703, which permits the safe administration of the doses necessary to mobilize these cells. AVM0703 is supplied as a sterile, single-use 50 mL, 24 mg/mL solution for infusion, without preservatives. The ability to rapidly mobilize and activate these cells following a single dose of AVM0703 in as little as 6 hours is the subject of an on-going clinical trial, in patients with lymphoid malignancies (NCT04329728), specifically no-option, R/R ALL, MCL, DLBCL, Primary Mediastinal Large B-cell, Burkitt, CLL/SLL and B-or T-ALL. The study consists of 2-parts, dose-escalation to determine the Phase 2 dose, followed by an adaptive-design, expansion cohort study in the same patient population. Concurrently, clinical data has also been obtained from Expanded Access-Single Patient INDs. Based on the murine model, a theoretically effective HED was determined to be at least 18 mg/kg. Because the maximum dose approved for generic injectable dexamethasone is 6 mg/kg, the starting dose for the clinical trial was set at 6 mg/kg. The dose escalation study design is a 3 x 3 design, originally consisting of cohorts escalating by 3 mg/kg to 21 mg/kg (6, 9, 12, 15, 18 and 21 mg/kg). Since that time and based on safety data (see below), the FDA has permitted a revision to the study, in which the 12 and 15 mg/kg cohorts are skipped. Table 1 provides the original and current study design, with the corresponding total dose for a 70 kg patient. For example, 18 mg/kg is 1.26 g for a 70 kg patient. The trial also incorporates a validated Quality of Life questionnaire and a 12-month follow-up period. In Expanded Use, Single-Patient IND setting, 4 patients received at least one AVM0703 dose: glioblastoma: one 6 mg/kg;B-cell ALL: one 18 mg/kg dose;and two prostate cancer patients: one 18 mg/kg dose and patient #2: repeat doses for the past year as depicted in Table 2. Figure 1 depicts the flow cytometry analysis 24 hours following an 18 mg/kg AVM0703 dose. From a safety perspective, there have been no reports of drug-related or treatment emergent SAE's. The murine model safety findings correlate to the human experience. Adverse events reported to date have been self-limiting and mild to moderate. Frequent AEs include slight elevations of blood pressure, glucose and BUN that resolve without treatment in < 1 week post dose. Leukocytosis and lymphocytosis were reported 24 hours post infusion from the B-cell ALL patient but resolved by 7-days without reported intervention. Because a single AVM0703 dose triggers the rapid mobilization and activation of an endogenous bi-specific gamma-delta+ NKT cell with a favorable emerging safety profile, AVM0703 shows promise as a therapeutic agent in treating this serious disease. [Formula presented] Disclosures: Rea: AVM Biotechnology, LLC: Current Employment. Deisher: AVM Biotechnology, LLC: Current Employment. Jarzyna: AVM Biotechnology, LLC: Current Employment. Zahid: AVM Biotechnology, LLC: Ended employment in the past 24 months. Suwito: AVM Biotechnology, LLC: Current Employment. Poulin: AVM Biotechnology, LLC: Current Employment.