Effect of homeostatic T-cell proliferation in the vaccine responsiveness against influenza in elderly people

Abstract

Background Seasonal influenza virus infection is a significant cause of morbimortality in the elderly. However, there is poor vaccine efficacy in this population due to immunosenescence. We aimed to explore several homeostatic parameters in the elderly that could impact influenza vaccine responsiveness. Methods Subjects (> 60 years old) who were vaccinated against influenza virus were included, and the vaccine response was measured by a haemagglutination inhibition (HAI) test. At baseline, peripheral CD4 and CD8 T-cells were phenotypically characterized. Thymic function and the levels of different inflammation-related biomarkers, including Lipopolysaccharide Binding Protein (LBP) and anti-cytomegalovirus (CMV) IgG antibodies, were also measured. Results Influenza vaccine non-responders showed a tendency of higher frequency of regulatory T-cells (Tregs) before vaccination than responders (1.49 [1.08–1.85] vs. 1.12 [0.94–1.63], respectively, p = 0.061), as well as higher expression of the proliferation marker Ki67 in Tregs and different CD4 and CD8 T-cell maturational subsets. The levels of inflammation-related biomarkers correlated with the frequencies of different proliferating T-cell subsets and with thymic function (e.g., thymic function with D-dimers, r = − 0.442, p = 0.001). Conclusions Age-related homeostatic dysregulation involving the proliferation of CD4 and CD8 T-cell subsets, including Tregs, was related to a limited responsiveness to influenza vaccination and a higher inflammatory status in a cohort of elderly people. Electronic supplementary material The online version of this article (10.1186/s12979-019-0154-y) contains supplementary material, which is available to authorized users.

Immunological features beyond CD4/CD8 ratio values in older individuals

“…Comorbid medical conditions, including cardiovascular diseases, metabolic disorders, bone/joint diseases, brain diseases, respiratory diseases, cancer, digestive diseases, genitourinary pathologies, dermatological diseases, and habits/addictions, were recorded at the time of sample collection for all the nursing home residents included in this study (for more detail on the type of events recorded, see ref. [ 48 ]). Furthermore, we evaluated the Barthel index for functional activities of daily living (ADL) as a disability degree parameter, in which 100 is assigned to a totally independent individual and <20 indicates totally dependent.…”

The Complex Role of Regulatory T Cells in Immunity and Aging

“…This is thought to be due to not only lower T cell activation but also to an accumulation of Treg which negatively affect the GC reaction ( 127 ). Along these lines, another study in aged patients showed that non-responder individuals to influenza vaccination have a higher frequency of Treg as well as a higher inflammatory status compared to responders ( 128 ). Depletion of Treg with anti-CD25 treatment prior to influenza infection protected against lethal viral challenge in aged mice ( 129 ).…”

Gal3 Plays a Deleterious Role in a Mouse Model of Endotoxemia

“…For flow cytometry, Prism, version 5.0 (GraphPad Software Inc., San Diego, CA, USA) was used for the generation of the graphs [63]. Statistical significance analysis was calculated using the Mann-Whitney U test.…”