NKG2D expression in CD4+ T lymphocytes as a marker of senescence in the aged immune system |
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Authors: | Rebeca Alonso-Arias Marco A Moro-García Antonio López-Vázquez Luis Rodrigo José Baltar Francisco M Suárez García Juan J Solano Jaurrieta Carlos López-Larrea |
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Institution: | 1.Histocompatibility Unit, Immunology Department,Hospital Universitario Central de Asturias,Oviedo,Spain;2.Gastroenterology Department,Hospital Universitario Central de Asturias,Oviedo,Spain;3.Health Outcomes Research Unit, Nephrology Department,Hospital Universitario Central de Asturias,Oviedo,Spain;4.Consejería de Salud y Servicios Sanitarios del Principado de Asturias,Oviedo,Spain;5.Internal Medicine and Geriatrics Department,Hospital Monte Naranco,Oviedo,Spain;6.Fundación Renal “I?igo Alvarez de Toledo”,Madrid,Spain |
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Abstract: | Human aging is characterized by changes in the immune system which have a profound impact on the T-cell compartment. These
changes are more frequently found in CD8+ T cells, and there are not well-defined markers of differentiation in the CD4+ subset.
Typical features of cell immunosenescence are characteristics of pathologies in which the aberrant expression of NKG2D in
CD4+ T cells has been described. To evaluate a possible age-related expression of NKG2D in CD4+ T cells, we compared their
percentage in peripheral blood from 100 elderly and 50 young adults. The median percentage of CD4+ NKG2D+ in elders was 5.3%
(interquartile range (IR): 8.74%) versus 1.4% (IR: 1.7%) in young subjects (p < 0.3 × 10−10). CD28 expression distinguished two subsets of CD4+ NKG2D+ cells with distinct functional properties and differentiation
status. CD28+ cells showed an immature phenotype associated with high frequencies of CD45RA and CD31. However, most of the
NKG2D+ cells belonged to the CD28null compartment and shared their phenotypical properties. NKG2D+ cells represented a more advanced stage of maturation and exhibited
greater response to CMV (5.3 ± 3.1% versus 3.4 ± 2%, p = 0.037), higher production of IFN-γ (40.56 ± 13.7% versus 24 ± 8.8%, p = 0.015), lower activation threshold and reduced TREC content. Moreover, the frequency of the CD4+ NKG2D+ subset was clearly
related to the status of the T cells. Higher frequencies of the NKG2D+ subset were accompanied with a gradual decrease of
NAIVE and central memory cells, but also with a higher level of more differentiated subsets of CD4+ T cells. In conclusion,
CD4+ NKG2D+ represent a subset of highly differentiated T cells which characterizes the senescence of the immune system. |
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Keywords: | Immunosenescence NKG2D CD4+ T lymphocytes Differentiation CMV |
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