Metabolic Reprogramming by the Excessive AMPK Activation Exacerbates Antigen-Specific Memory CD8⁺ T Cell Differentiation after Acute Lymphocytic Choriomeningitis Virus Infection

During virus infection, T cells must be adapted to activation and lineage differentiation states via metabolic reprogramming. Whereas effector CD8⁺ T cells preferentially use glycolysis for their rapid proliferation, memory CD8⁺ T cells utilize oxidative phosphorylation for their homeostatic maintenance. Particularly, enhanced AMP-activated protein kinase (AMPK) activity promotes the memory T cell response through different pathways. However, the level of AMPK activation required for optimal memory T cell differentiation remains unclear. A new metformin derivative, IM156, formerly known as HL156A, has been reported to ameliorate various types of fibrosis and inhibit in vitro and in vivo tumors by inducing AMPK activation more potently than metformin. Here, we evaluated the in vivo effects of IM156 on antigen-specific CD8⁺ T cells during their effector and memory differentiation after acute lymphocytic choriomeningitis virus infection. Unexpectedly, our results showed that in vivo treatment of IM156 exacerbated the memory differentiation of virus-specific CD8⁺ T cells, resulting in an increase in short-lived effector cells but decrease in memory precursor effector cells. Thus, IM156 treatment impaired the function of virus-specific memory CD8⁺ T cells, indicating that excessive AMPK activation weakens memory T cell differentiation, thereby suppressing recall immune responses. This study suggests that metabolic reprogramming of antigen-specific CD8⁺ T cells by regulating the AMPK pathway should be carefully performed and managed to improve the efficacy of T cell vaccine.

MENINGOCOCCAL AND TRAVELLERS’ VACCINATIONS

The increase in international tourism has created demandfor vaccination to protect against travel-associatedillness. The decision to vaccinate travellers involvesrisk-benefit assessment. Most currently used travelvaccines include the meningococcal vaccine, yellow fevervaccine, typhoid vaccine, and Japanese encephalitisvaccine.This review addresses the limitations posed by themeningococcal polysaccharide vaccine, the differentquadrivalent meningococcal conjugate vaccines available,the current recommendations in children and adults andthe development of new meningococcal B vaccines.This review also addresses the current recommendationsfor yellow fever vaccines, new typhoid conjugate vaccines,changing epidemiology of Japanese encephalitis (JE), andnew recommendations for the JE vaccines.

Aplicación de la nanobiotecnología con el sistema CRISPR-cas / Application of the nanobiotechnology with the system CRISP-Cas

Resumen Introducción: La nanobiotecnología y la biología sintética son ciencias que impactan en la actualidad con el lanzamiento de aplicaciones innovadoras y beneficiosas para el ser humano, estas ciencias se han fusionado para fabricar nuevos componentes para la construcción de células totalmente artificiales y la creación de biomoléculas sintéticas. Objetivo: Conocer las aplicaciones de la nanobiotecnología relacionadas con el uso del sistema CRISPR/Cas en el almacenamiento de información en el ADN bacteriano y alternativas terapéuticas. Materiales y métodos: Se realizó una revisión bibliográfica sobre las principales aplicaciones de la nanobiotecnología, en las bases de datos ScienceDirect, SciELO, PubMed y en revistas como: Nature biotechnology, Biochemistry, Science y Journal Microbiology. Resultados: La revisión de literatura describe y analiza las nuevas aplicaciones nanobiotecnológicas utilizadas para escribir información en el código genético de las células bacterianas, en el que se emplean el sistema basado en repeticiones palindrómicas cortas agrupadas y regularmente interespaciadas (CRISPR/Cas) y la producción de ADN sintético, así como las alternativas terapéuticas relacionadas con la terapia génica. Conclusión: Entre las aplicaciones nanobiotecnológicas se han demostrado dos métodos para grabar información en el ADN de células bacterianas, de Escherichia coli y Sulfolobus tokodai vinculados con el empleo del sistema CRISPR/Cas y la producción de ADN sintético, así como el uso del CRISPR/Cas en la terapia génica y celular.

Abstract Introduction: Nanobiotechnology and synthetic biology are sciences that impact today with the launching of innovative and beneficial applications for the human being. These sciences have been amalgamated to manufacture new components for the construction of totally artificial cells and the creation of synthetic biomolecules. Objective: To know the applications of nanobiotechnology related to the use of the system CRISPR/Cas in the storage of bacterial DNA and therapeutic alternatives. Materials and methods: A bibliographical review on the main applications of nanobiotechnology was carried out in ScienceDirect, SciELO, PubMed databases and in magazines such as: Nature Biotechnology, Biochemistry, Science and Journal Microbiology. Results: The literature review describes and analyzes the new nanobiotechnology applications used to write information in the genetic code of bacterial cells, in which the system is used based on short grouped and regularly interspaced palindromic repetitions (CRISPR/Cas) and the production of synthetic DNA, as well as therapeutic alternatives related to gene therapy. Conclusion: Among the nanobiotechnology applications, two methods to record information in the DNA of bacterial cells Escherichia coli and Sulfolobus Tokodai have been shown, which are linked to the use of the system CRISPR/Cas and the production of synthetic DNA, as well as the use of CRISPR/Cas in gene and cellular therapy.

Inmunodeficiencia común variable: caracterización clínica e inmunológica de pacientes e identificación de subgrupos homogéneos con base en la tipificación de subpoblaciones de linfocitos B / Common variable immunodeficiency: Clinical and immunological characterization of patients and homogeneous subgroup definition by means of B lymphocyte subpopulation typing

Introducción. La inmunodeficiencia común variable es un síndrome heterogéneo caracterizado por infecciones recurrentes, hipogammaglobulinemia y producción deficiente de anticuerpos específicos. Las anormalidades en subpoblaciones de linfocitos en sangre periférica, particularmente de linfocitos B, permiten la clasificación de los pacientes en grupos homogéneos. Objetivo. Caracterizar clínica e inmunológicamente los linfocitos B y tipificar sus subpoblaciones en doce pacientes colombianos con inmunodeficiencia común variable, para clasificarlos en grupos homogéneos. Materiales y métodos. Se revisaron las historias clínicas de los pacientes y se evaluaron las inmunoglobulinas séricas, la proliferación de linfocitos y la hipersensibilidad retardada, así como las subpoblaciones de linfocitos y de linfocitos B mediante citometría de flujo. Resultados. Todos los pacientes presentaron infecciones respiratorias o gastrointestinales recurrentes y, algunos, infecciones en otros sistemas. Además, todos presentaban disminución de la IgG, en tanto que la IgA y la IgM fueron bajas en nueve y diez pacientes, respectivamente. En todos hubo disminución de la proliferación de linfocitos inducida por mitógenos, pero fue normal frente a antígenos específicos. La tipificación de subpoblaciones reveló valores elevados de linfocitos T en tres pacientes; siete presentaron disminución en la relación CD4+/CD8+ y, cuatro, linfocitos NK bajos. El conteo de linfocitos B fue normal en once pacientes, ocho de los cuales presentaron linfocitos B de memoria bajos, en tanto que cuatro presentaron aumento de linfocitos B de transición o de linfocitos B CD21 low . Conclusión. La tipificación de subpoblaciones de linfocitos solo permitió asignar a 11 de los pacientes a grupos homogéneos según los esquemas de clasificación internacionales, lo que indica la necesidad de agregar más criterios hasta lograr una clasificación ideal. Este estudio permitirá establecer mejores seguimientos médicos para pacientes con inmunodeficiencia común variable en grupos con alto riesgo de desarrollar complicaciones clínicas.

Introduction: Common variable immunodeficiency is a heterogeneous syndrome characterized by recurrent infections, hypogammaglobulinemia and defective production of specific antibodies. Abnormalities in peripheral blood lymphocyte subpopulations, in particular of B lymphocytes, allow the classification of patients into homogeneous groups. Objective: To perform a clinical and immunological characterization and to evaluate lymphocyte subpopulations of twelve Colombian patients with common variable immunodeficiency in order to define homogeneous groups. Materials and methods: We reviewed medical records and evaluated serum immunoglobulins (Ig), lymphoproliferation, delayed hypersensitivity and used flow cytometry to quantify peripheral blood total lymphocyte and B cell populations. Results: All patients had recurrent respiratory and/or gastrointestinal infections, while some also had infections affecting other systems. All patients had abnormally low serum IgG levels, while IgA and IgM levels were reduced in nine and ten patients, respectively. Lymphoproliferation to mitogen was lower in patients than in healthy controls but lymphoproliferation to specific antigen was normal in all. Flow cytometry revealed high numbers of T cells in three patients, while seven had a low CD4+/CD8+ ratio and four had reduced NK cells . Eleven patients had normal B cell counts, and eight of them also showed decreased memory B lymphocytes, and four had increased transitional or CD21 low B lymphocytes. Conclusion: Lymphocyte typing allowed assigning all but one patient to homogeneous groups according to international classification schemes, indicating the necessity of including more criteria until an ideal classification is achieved. This study will lead to a better medical monitoring of common variable immunodeficiency patients in groups at high risk of developing clinical complications.

Involvement of memory T-cells in the pathophysiology of chronic lymphocytic leukemia

The role of T-cells in the pathogenesis of chronic lymphocytic leukemia has recently gained much attention due to the importance of the constant interaction between neoplastic B-cells with microenvironment substratum and T-cells. It is believed that these interactions modulate the clinical course of the disease, mainly through the regulation of the expansion, differentiation, and survival of chronic lymphocytic leukemia B-cells. Importantly, this crosstalk may also change the number, function, and memory phenotype of normal T-cells, thereby altering the amplitude and/or efficiency of adaptive immunity in chronic lymphocytic leukemia patients. The present study presents an overview on important aspects of this immunological crosstalk, particularly on the abnormalities of chronic lymphocytic leukemia B-cells and the alterations in normal T-cells, with focus on the CD4 memory T-cell compartment that could offer survival signals to chronic lymphocytic leukemia B-cell clone(s) and contribute to the establishment and progression of the disease. The authors believe that understanding the biological consequences of the interaction between normal T- and neoplastic B-cells in chronic lymphocytic leukemia may allow for improvements in the prognostic information and therapeutic approaches for this disease.

In Vivo Kinetics and Biodistribution of a Hantaan Virus DNA Vaccine after Intramuscular Injection in Mice / 中国病毒学·英文版

To study the kinetics in vivo of a Hantaan virus DNA vaccine, we constructed a fusion DNA vaccine,pEGFP/S, by cloning the S segment of Hantavirus into the vector, pEGFP-C1, which encodes Green fluorescent protein EGFP. In this report, we provide evidence that pEGFP/S was distributed and persistently expressed for more than 60 days in several organs after inoculation. Our findings suggest that the persistent immune responses induced by a Hantaan virus DNA vaccine are likely due to the plasmid pEGFP/S deposited in vivo, which acts as a booster immunization.

A study of the current(2003-2005) prevalence of anti-HBs and immunologic memory of hepatitis B vaccine in children from the central area of Korea / 소아과

PURPOSE: This study was conducted to assess the current(2003-2005) prevalence of anti-HBs and immunologic memory for Hepatitis B vaccine in children from the central area of Korea. METHODS: Subjects were chosen from children and adolescents who received tests for hepatitis B surface antigen(HBsAg) and anti-HBs at Dankook University Hospital from March 2003 to May 2005. Among these, antibodies to hepatitis B core antigen(IgG anti-HBc) were checked. A single booster vaccination was performed on children whose anti-HBs titers were under 10 mIU/mL. One month after booster vaccination we rechecked the anti-HBs titer. RESULTS: A total of 3,277 subjects were tested for HBsAg/anti-HBs, and 1,913(58.4 percent) of them were positive for anti-HBs. Of these, 29 subjects(0.9 percent) were positive for HBsAg. Positive results for anti-HBs by age were 78.6 percent for 6-12 months of age, 62.7 percent for 1-3 years of age, 51.9 percent for 4-6 years of age, 49.5 percent for 7-12 years of age, 63.4 percent for 13-15 years of age and 72.2 percent for 16-18 years of age. The 80 subjects who were tested negative for HBsAg/anti-HBs received a single booster vaccine, 71 subjects were tested positive for antibodies. IgG anti-HBc titer was checked for 169 of the subjects, 5 subjects were positive. CONCLUSION: In our study, a significant anamnestic response was observed in 88.8 percent of children. This is believed to be a result of the relatively long immunologic memory effect of the hepatitis B vaccination in children from the central area of Korea.

Comparison of memory B cell polyclonal activation by different phylogeny antigens / 中国免疫学杂志

Objective:To characterize the memory B lymphocytes activalion by nonspecific antigen of different phylogeny antigen.Methods:Three groups were immunized by same quantity different antigens,which were ovalbumin,milk and ostrcean extract to intitule A,B,C,respectively,as basic immunity.After one week,across immunity was performed with A,B and C antigen as secondary immunity,the subgroups were divided.Basic antibodies were determined with ELISA before and after secondary immunity.Results:Antibodies after secondary immunity increase 10%～25% than that before secondary immunity in subgroups which antigens were different when basic and secondary immunity.There were significant difference compare with control groups (P