Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 6 de 6
Filtrar
1.
Immunology ; 135(1): 27-39, 2012 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-22044339

RESUMEN

Cytomegalovirus (CMV) infection and reactivation pose a serious threat for patients after haematopoietic stem cell transplantation. We have previously shown that CD8(+) T cells targeting different CMV epitopes correlate with protection at different threshold frequencies in those patients. To investigate if this may relate to a different quality of these cells here we analyse the T-cell receptor diversity of pp50 (245-253)/HLA-A*0101 specific CD8(+) T cells with that of CD8(+) T cells targeting various pp65 peptides. The results from this pilot study show differences in the breadth of the T-cell receptor usage of the different cell populations. We observe for the first time that the T-cell receptor Vß CDR3 spectratypes used by CMV pp50 (245-253)/HLA-A*0101-specific CD8(+) T cells can reach higher numbers than those used by CD8(+) T cells targeting various pp65 peptides in our patient cohort. This merits further investigation into the effectiveness of the different CMV-specific T cells and their impact on immunosenescence, which is important to eventually define the most useful source of adoptive therapy and monitoring protocols for cytomegalovirus-specific immune responses.


Asunto(s)
Linfocitos T CD8-positivos/inmunología , Infecciones por Citomegalovirus/inmunología , Citomegalovirus/inmunología , Antígeno HLA-A1/inmunología , Complejo Receptor-CD3 del Antígeno de Linfocito T/inmunología , Receptores de Antígenos de Linfocitos T alfa-beta/inmunología , Adulto , Estudios de Cohortes , Proteínas de Unión al ADN/inmunología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Péptidos/inmunología , Fosfoproteínas/inmunología , Proyectos Piloto , Proteínas de la Matriz Viral/inmunología , Proteínas Virales/inmunología
2.
Br J Haematol ; 148(2): 311-322, 2010 Jan 01.
Artículo en Inglés | MEDLINE | ID: mdl-19895611

RESUMEN

Cytomegalovirus (CMV) causes significant morbidity and mortality in patients after haematopoietic stem cell transplantation (HSCT). Due to limitations of current antiviral therapies, alternative approaches, involving transfer of donor-derived CMV-specific CD8(+) T cells, have been considered. Levels of such cells correlating with protection against CMV infection and disease have only been reported in patients expressing HLA-A*0201 and HLA-B*0702. This is despite an increasing number of reports describing cells targeting CMV peptides presented by other human leucocyte antigens (HLAs). Considering several frequent HLA alleles, our findings suggest that HLA-A*2402/pp65 (341-349)- and HLA-B*3501/pp65 (123-131)-specific CD8(+) T cells correlate with protection from CMV reactivation at significantly lower cell levels than HLA-A*0101/pp50 (245-253)- and HLA-A*0201/pp65 (495-503)-specific CD8(+) T cells, both in HSCT recipients post-transplant and in healthy CMV seropositive volunteers. This may result from a differing efficiency of the responses restricted by the two sets of HLA alleles. These findings add to the knowledge of immunodominance and differences in antigen processing that are coordinated in individuals with different HLA alleles and have direct implications for therapy and monitoring in patients.

3.
Br J Haematol ; 148(2): 311-22, 2010 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-20095088

RESUMEN

Cytomegalovirus (CMV) causes significant morbidity and mortality in patients after haematopoietic stem cell transplantation (HSCT). Due to limitations of current antiviral therapies, alternative approaches, involving transfer of donor-derived CMV-specific CD8(+) T cells, have been considered. Levels of such cells correlating with protection against CMV infection and disease have only been reported in patients expressing HLA-A*0201 and HLA-B*0702. This is despite an increasing number of reports describing cells targeting CMV peptides presented by other human leucocyte antigens (HLAs). Considering several frequent HLA alleles, our findings suggest that HLA-A*2402/pp65 (341-349)- and HLA-B*3501/pp65 (123-131)-specific CD8+ T cells correlate with protection from CMV reactivation at significantly lower cell levels than HLA-A*0101/pp50 (245-253)- and HLAA* 0201/pp65 (495-503)-specific CD8+ T cells, both in HSCT recipients posttransplant and in healthy CMV seropositive volunteers. This may result from a differing efficiency of the responses restricted by the two sets of HLA alleles. These findings add to the knowledge of immunodominance and differences in antigen processing that are coordinated in individuals with different HLA alleles and have direct implications for therapy and monitoring in patients.


Asunto(s)
Antígenos Virales/inmunología , Linfocitos T CD8-positivos/inmunología , Infecciones por Citomegalovirus/inmunología , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Adolescente , Adulto , Antígenos Virales/genética , Antivirales/uso terapéutico , Infecciones por Citomegalovirus/tratamiento farmacológico , Infecciones por Citomegalovirus/genética , Citotoxicidad Inmunológica/genética , Citotoxicidad Inmunológica/inmunología , Femenino , Citometría de Flujo , Ganciclovir/uso terapéutico , Antígenos HLA-A/genética , Antígeno HLA-A2 , Antígenos HLA-B/genética , Antígeno HLA-B7 , Enfermedades Hematológicas/terapia , Enfermedades Hematológicas/virología , Humanos , Masculino , Persona de Mediana Edad , Carga Viral , Adulto Joven
4.
Transpl Immunol ; 35: 1-6, 2016 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-26836476

RESUMEN

BACKGROUND: Regulatory B (Breg) and T (Treg) cells represent a biomarker for tolerance in transplant patients. Despite the importance of Treg and Breg in transplantation and the suggested crosstalk between both suppressive cell populations, little is known on how they are influenced by long-term immunosuppressive treatment. The aim of the present study was to investigate the effect of different immunosuppressive drugs used in routine clinical practice on Treg and Breg cell numbers. METHODS: Thirty-six kidney transplant recipients with stable graft function were recruited and classified according to their concomitant therapy: 22 patients received calcineurin inhibitors (CNI) and 14 patients received mammalian target of rapamycin (mTOR) inhibitors. A group of 8 healthy untreated subjects was included as control. Absolute numbers of peripheral blood-derived IL10-producing B cells (CD19(+)IL10(+)), CD19(+)CD24(hi)CD38(hi) transitional B cells and Treg cells (CD4(+)CD25(+)FOXP3(+)) were quantified in all KT patients and controls by flow cytometry. RESULTS: CD19(+)CD24(hi)CD38(hi) transitional B cells increased over time and seem to be related with long-term therapeutic graft survival irrespective of the treatment regimen. CNI and mTOR inhibitors significantly reduced numbers of Breg cells when compared with healthy individuals, whereas mTOR inhibitors expanded Treg cells in comparison with CNI drugs. CONCLUSIONS: Bridging the drug-mediated reduction of Breg cell numbers in vivo with the requirements of Breg cells for long-term transplant success remains an as yet unresolved task for therapeutic intervention. Further larger cohort studies that evaluate the effect of different treatment regimen on defined lymphocyte subpopulations are warranted.


Asunto(s)
Linfocitos B Reguladores/inmunología , Inhibidores de la Calcineurina/administración & dosificación , Trasplante de Riñón , Linfocitos T Reguladores/inmunología , Serina-Treonina Quinasas TOR/antagonistas & inhibidores , Inmunología del Trasplante/efectos de los fármacos , Antígenos CD/inmunología , Femenino , Humanos , Interleucina-10/inmunología , Masculino , Serina-Treonina Quinasas TOR/inmunología
5.
Math Biosci Eng ; 9(4): 699-736, 2012 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-23311419

RESUMEN

Some key features of a mathematical description of an immune response are an estimate of the number of responding cells and the manner in which those cells divide, differentiate, and die. The intracellular dye CFSE is a powerful experimental tool for the analysis of a population of dividing cells, and numerous mathematical treatments have been aimed at using CFSE data to describe an immune response [30,31,32,37,38,42,48,49]. Recently, partial differential equation structured population models, with measured CFSE fluorescence intensity as the structure variable, have been shown to accurately fit histogram data obtained from CFSE flow cytometry experiments [18,19,52,54]. In this report, the population of cells is mathematically organized into compartments, with all cells in a single compartment having undergone the same number of divisions. A system of structured partial differential equations is derived which can be fit directly to CFSE histogram data. From such a model, cell counts (in terms of the number of divisions undergone) can be directly computed and thus key biological parameters such as population doubling time and precursor viability can be determined. Mathematical aspects of this compartmental model are discussed, and the model is fit to a data set. As in [18,19], we find temporal and division dependence in the rates of proliferation and death to be essential features of a structured population model for CFSE data. Variability in cellular autofluorescence is found to play a significant role in the data, as well. Finally, the compartmental model is compared to previous work, and statistical aspects of the experimental data are discussed.


Asunto(s)
Fluoresceínas , Interpretación de Imagen Asistida por Computador/métodos , Recuento de Linfocitos/métodos , Linfocitos/citología , Linfocitos/fisiología , Microscopía Fluorescente/métodos , Modelos Biológicos , Succinimidas , Animales , División Celular/fisiología , Proliferación Celular , Simulación por Computador , Humanos
6.
J Immunol Methods ; 373(1-2): 143-60, 2011 Oct 28.
Artículo en Inglés | MEDLINE | ID: mdl-21889510

RESUMEN

CFSE analysis of a proliferating cell population is a popular tool for the study of cell division and divisionlinked changes in cell behavior. Recently Banks et al. (2011), Luzyanina et al. (2009), Luzyanina et al. (2007), a partial differential equation (PDE) model to describe lymphocyte dynamics in a CFSE proliferation assay was proposed. We present a significant revision of this model which improves the physiological understanding of several parameters. Namely, the parameter used previously as a heuristic explanation for the dilution of CFSE dye by cell division is replaced with a more physical component, cellular autofluorescence. The rate at which label decays is also quantified using a Gompertz decay process. We then demonstrate a revised method of fitting the model to the commonly used histogram representation of the data. It is shown that these improvements result in a model with a strong physiological basis which is fully capable of replicating the behavior observed in the data.


Asunto(s)
Proliferación Celular , Fluoresceínas/metabolismo , Modelos Biológicos , Succinimidas/metabolismo , Algoritmos , División Celular , Citometría de Flujo , Colorantes Fluorescentes/metabolismo , Humanos , Cinética , Leucocitos Mononucleares/citología , Leucocitos Mononucleares/metabolismo , Linfocitos/citología , Linfocitos/metabolismo , Simulación de Dinámica Molecular
SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA