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Resumen: Introducción: La neuroinflamación está involucrada en la fisiopatología de diferentes trastornos neurológicos, en particular la enfermedad de Alzheimer (EA) y la enfermedad de Parkinson (EP). Las alteraciones en la barrera hematoencefálica pueden permitir la entrada al sistema nervioso central de linfocitos periféricos, los cuales pueden participar en la patología de las enfermedades. Objetivo: Evaluar el perfil de linfocitos periféricos en pacientes con EA y EP y su asociación con la enfermedad y su progresión. Métodos: Se incluyeron 20 pacientes con EA, 20 pacientes con EP y un grupo de individuos sanos. Diez de los pacientes con EA y 12 de los pacientes con EP fueron evaluados una segunda vez de 17 a 27 meses después del inicio del estudio. Las subpoblaciones de linfocitos y su estado de activación se determinaron mediante citometría de flujo. Todos los pacientes fueron evaluados neurológicamente utilizando escalas validadas internacionalmente. Resultados: Los pacientes con EA y EP mostraron un aumento significativo en los niveles de linfocitos activados, linfocitos susceptibles a la apoptosis, células T de memoria central y células T y B reguladoras con respecto a los sujetos sanos. A medida que las enfermedades progresaron se observó una disminución significativa de las células activadas (CD4+ CD38+ y CD8+ CD38+ en EP y EA; CD4+ CD69+ y CD8+ CD69+ en EP), de las células T susceptibles a la apoptosis y de algunas poblaciones reguladoras (CD19+ CD5+ IL10+ en EP y EA; CD19+ CD5+ IL10+ FoxP3+, CD4+ FoxP3+ CD25+ CD45RO+ en EP). En pacientes con EA la progresión de la enfermedad se asoció con porcentajes más bajos de CD4 + CD38 + y mayores porcentajes de células CD4 efectoras al comienzo del estudio. Se observaron diferencias significativas entre ambas enfermedades. Conclusiones: Este estudio proporciona evidencia de cambios en los fenotipos de linfocitos periféricos asociados a EA y EP y a su gravedad. Teniendo en cuenta la comunicación efectiva sangre-cerebro, nuestros resultados abren nuevas vías para explorar terapias de inmunomodulación para tratar estas enfermedades. Abstract: Introduction: Neuroinflammation is involved in the pathophysiology of various neurological disorders, in particular Alzheimer disease (AD) and Parkinson's disease (PD). Alterations in the blood-brain barrier may allow peripheral blood lymphocytes to enter the central nervous system; these may participate in disease pathogenesis. Objective: To evaluate the peripheral blood lymphocyte profiles of patients with AD and PD and their association with the disease and its progression. Methods: The study included 20 patients with AD, 20 with PD, and a group of healthy individuals. Ten of the patients with AD and 12 of those with PD were evaluated a second time 17 to 27 months after the start of the study. Lymphocyte subpopulations and their activation status were determined by flow cytometry. All patients underwent neurological examinations using internationally validated scales. Results: Compared to healthy individuals, patients with AD and PD showed significantly higher levels of activated lymphocytes, lymphocytes susceptible to apoptosis, central memory T cells, and regulatory T and B cells. As the diseases progressed, there was a significant decrease in activated cells (CD4+ CD38+ and CD8+ CD38 + in PD and AD, CD4+ CD69+ and CD8+ CD69+ in PD), T cells susceptible to apoptosis, and some regulatory populations (CD19+ CD5+ IL10+ in PD and AD, CD19+ CD5+ IL10+ FoxP3+, CD4+ FoxP3+ CD25+ CD45RO+ in PD). In patients with AD, disease progression was associated with lower percentages of CD4+ CD38+ cells and higher percentages of effector CD4 cells at the beginning of the study. Significant differences were observed between both diseases. Conclusions: This study provides evidence of changes in peripheral blood lymphocyte phenotypes associated with AD and PD and their severity. Considering effective blood-brain communication, our results open new avenues of research into immunomodulation therapies to treat these diseases.

Introduction: Neuroinflammation is involved in the pathophysiology of various neurological disorders, in particular Alzheimer disease (AD) and Parkinson's disease (PD). Alterations in the blood-brain barrier may allow peripheral blood lymphocytes to enter the central nervous system; these may participate in disease pathogenesis., Objective: To evaluate the peripheral blood lymphocyte profiles of patients with AD and PD and their association with the disease and its progression., Methods: The study included 20 patients with AD, 20 with PD, and a group of healthy individuals. Ten of the patients with AD and 12 of those with PD were evaluated a second time 17 to 27 months after the start of the study. Lymphocyte subpopulations and their activation status were determined by flow cytometry. All patients underwent neurological examinations using internationally validated scales., Results: Compared to healthy individuals, patients with AD and PD showed significantly higher levels of activated lymphocytes, lymphocytes susceptible to apoptosis, central memory T cells, and regulatory T and B cells. As the diseases progressed, there was a significant decrease in activated cells (CD4+ CD38+ and CD8+ CD38+ in PD and AD, CD4+ CD69+ and CD8+ CD69+ in PD), T cells susceptible to apoptosis, and some regulatory populations (CD19+ CD5+ IL10+ in PD and AD, CD19+ CD5+ IL10+ FoxP3+, CD4+ FoxP3+ CD25+ CD45RO+ in PD). In patients with AD, disease progression was associated with lower percentages of CD4+ CD38+ cells and higher percentages of effector CD4 cells at the beginning of the study. Significant differences were observed between both diseases., Conclusions: This study provides evidence of changes in peripheral blood lymphocyte phenotypes associated with AD and PD and their severity. Considering effective blood-brain communication, our results open new avenues of research into immunomodulation therapies to treat these diseases., (Copyright © 2019 Sociedad Española de Neurología. Published by Elsevier España, S.L.U. All rights reserved.)

T regulatory cells play a key role in the control of the immune response, both in health and during illness. While the mechanisms through which T regulatory cells exert their function have been extensively described, their molecular effects on effector cells have received little attention. Thus, this revision is aimed at summarizing our current knowledge on those regulation mechanisms on the target cells from a molecular perspective.