RESUMEN
INTRODUCTION: Chronic lymphocytic leukemia is usually diagnosed through the characteristic morphology/immunophenotype of the lymphocytes, but some CLL cases remain atypical resulting in diagnostic uncertainty. METHODS: Using flow cytometry analysis, we investigated the expression of CDs160/200 on B cells from 124 patients (82 CLL, 42 other B-cell neoplasms) and nine controls. CDs160/200 measurements were determined as a ratio of the mean fluorescence intensities of leukemic cells/controls and were considered positive when the ratios were ≥2 and 20, respectively. RESULTS: Sixty and 83% CLL expressed CDs160/200 as compared to 5% and 10% of other B-cell neoplasms, respectively. None of the controls showed CDs160/200 expressions. Combination of both markers was observed in 55% of CLL but only in 2% of other B-cell neoplasms, and absence of both markers occurred in 12% of CLL but in 86% of other B-cell neoplasms. CONCLUSION: CDs160/200 were associated with markers of the gold standard 'Matutes score' and could be useful markers to differentiate atypical CLL from other B-cell neoplasms in the absence of available biopsies or cytogenetics and molecular studies.
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Antígenos CD/genética , Biomarcadores de Tumor/genética , Leucemia Linfocítica Crónica de Células B/diagnóstico , Receptores Inmunológicos/genética , Adulto , Anciano , Anciano de 80 o más Años , Antígenos CD/inmunología , Linfocitos B/inmunología , Linfocitos B/patología , Biomarcadores de Tumor/inmunología , Estudios de Casos y Controles , Diagnóstico Diferencial , Proteínas Ligadas a GPI/genética , Proteínas Ligadas a GPI/inmunología , Expresión Génica , Humanos , Leucemia de Células Pilosas/diagnóstico , Leucemia de Células Pilosas/genética , Leucemia de Células Pilosas/inmunología , Leucemia de Células Pilosas/patología , Leucemia Linfocítica Crónica de Células B/genética , Leucemia Linfocítica Crónica de Células B/inmunología , Leucemia Linfocítica Crónica de Células B/patología , Linfocitosis/diagnóstico , Linfocitosis/genética , Linfocitosis/inmunología , Linfocitosis/patología , Linfoma de Células B de la Zona Marginal/diagnóstico , Linfoma de Células B de la Zona Marginal/genética , Linfoma de Células B de la Zona Marginal/inmunología , Linfoma de Células B de la Zona Marginal/patología , Linfoma Folicular/diagnóstico , Linfoma Folicular/genética , Linfoma Folicular/inmunología , Linfoma Folicular/patología , Linfoma de Células del Manto/diagnóstico , Linfoma de Células del Manto/genética , Linfoma de Células del Manto/inmunología , Linfoma de Células del Manto/patología , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Curva ROC , Receptores Inmunológicos/inmunologíaRESUMEN
Apoptotic leukocytes are endowed with immunomodulatory properties that can be used to enhance hematopoietic engraftment and prevent graft-versus-host disease (GvHD). This apoptotic cell-induced tolerogenic effect is mediated by host macrophages and not recipient dendritic cells or donor phagocytes present in the bone marrow graft as evidenced by selective cell depletion and trafficking experiments. Furthermore, apoptotic cell infusion is associated with TGF-beta-dependent donor CD4+CD25+ T-cell expansion. Such cells have a regulatory phenotype (CD62L(high) and intracellular CTLA-4+), express high levels of forkhead-box transcription factor p3 (Foxp3) mRNA and exert ex vivo suppressive activity through a cell-to-cell contact mechanism. In vivo CD25 depletion after apoptotic cell infusion prevents the apoptotic cell-induced beneficial effects on engraftment and GvHD occurrence. This highlights the role of regulatory T cells in the tolerogenic effect of apoptotic cell infusion. This novel association between apoptosis and regulatory T-cell expansion may also contribute to preventing deleterious autoimmune responses during normal turnover.
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Apoptosis/inmunología , Bazo/citología , Bazo/inmunología , Linfocitos T Reguladores/inmunología , Factor de Crecimiento Transformador beta/metabolismo , Traslado Adoptivo , Animales , Trasplante de Médula Ósea/inmunología , Células Dendríticas/inmunología , Factores de Transcripción Forkhead/genética , Supervivencia de Injerto/inmunología , Enfermedad Injerto contra Huésped/prevención & control , Tolerancia Inmunológica , Técnicas In Vitro , Macrófagos/inmunología , Masculino , Ratones , Ratones Endogámicos BALB C , Ratones Endogámicos C57BL , Ratones Transgénicos , ARN Mensajero/genética , Receptores de Interleucina-2/metabolismoAsunto(s)
Apoptosis/fisiología , Fibroblastos/fisiología , Glicoproteínas de Membrana/fisiología , Transducción Genética , Transfección , Receptor fas/metabolismo , Células 3T3 , Animales , Antígenos CD34/metabolismo , Apoptosis/genética , Proteína Ligando Fas , Kanamicina Quinasa/genética , Kanamicina Quinasa/fisiología , Glicoproteínas de Membrana/genética , Ratones , Retroviridae/genética , Transducción Genética/métodos , Regulación hacia ArribaRESUMEN
BACKGROUND: The use of donor T cells expressing the herpes simplex thymidine kinase (HSV-TK) gene followed by ganciclovir (GCV) treatment could allow for specific modulation of the alloreactivity occurring after bone marrow transplantation. We are presently exploring such an approach in a phase I clinical trial. METHODS: To examine the beneficial effect of administrating HSV-TK-expressing donor T lymphocytes +/- GCV treatment on acute graft-versus-host disease (aGVHD) control, irradiated Balb/c or C57BL/6 mice underwent transplantation with allogeneic bone marrow cells in conjunction with CD3+ allogeneic splenocytes from transgenic mice expressing an HSV-TK transgene. GCV treatment was initiated upon the occurrence of severe aGVHD. RESULTS: GCV treatment resulted in a 40-60% long-term survival rate of GVHD-free recipients having received HSV-TK-expressing T cells, whereas only 0-6% of mice survived without GCV treatment. Lethal aGVHD occurred in all the control animals having received non-HSV-TK-expressing T cells, irrespective of GCV treatment. CONCLUSION: Our results demonstrate that the administration of donor HSV-TK-expressing T cells to hematopoietic stem cell graft recipients followed by GCV treatment at the onset of severe aGVHD significantly reduces aGVHD-induced mortality and results in GVHD-free surviving recipients.