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ToWards Immunisations that Last: the Immunology and Gerontology of Helper T cells

Descripción del proyecto

Aumentar la eficacia de las vacunas en las poblaciones envejecidas

A lo largo de los años, la disminución de muchas enfermedades infecciosas y de las muertes relacionadas con ellas puede atribuirse al significativo efecto de la vacunación. Sin embargo, a medida que las personas envejecen, su sistema inmunitario se debilita, lo cual aumenta su vulnerabilidad frente a infecciones y reduce su capacidad para beneficiarse de las vacunas. ¿La respuesta a la vacunación es irreversible o puede mejorarse? El equipo del proyecto TWILIGHT, financiado por el Consejo Europeo de Investigación, pretende comprender los mecanismos subyacentes de este declive y desarrollar estrategias para mejorar la eficacia de la vacunación. Los investigadores estudiarán los linfocitos T y las células presentadoras de antígenos en personas mayores para descifrar los mecanismos celulares y moleculares responsables de la respuesta subóptima a las vacunas.

Objetivo

A major accomplishment of modern society is the extension of human life expectancy. However, this creates a new challenge for medical science, to facilitate healthy ageing. With age, the function of the immune system declines, rendering older people more susceptible to infections and less able to benefit from vaccination. Indeed, improving vaccine efficacy is key to reducing infection-related morbidity in older people. To date, the complexity of the ageing process has hindered attempts to fulfil this ambition, and thus innovative approaches are required to better understand the underlying biology.

Vaccination creates protective immunity by inducing the germinal centre (GC) response, an intricate process that generates memory B cells and long-lived antibody-secreting plasma cells. However, the GC response declines with age. Strikingly, it is not B cells that are responsible for the age-dependent decline in the GC response, but the CD4+ T cells and the microenvironment of older individuals. The cellular and molecular mechanisms responsible, however, remain unknown. In the GC there are two subsets of specialised CD4+ T cells, T follicular helper (Tfh) and T follicular regulatory (Tfr) cells, which act in opposition to promote and suppress the response, respectively. I hypothesise that aberrant formation and/or function of Tfh and Tfr cells contribute to impaired GC responses during ageing, and that these cells could be targeted to improve vaccine efficacy. Furthermore, the most prominent age-dependent change in secondary lymphoid tissues is the accumulation of senescent cells, which can modify immune function and tissue structure. I hypothesise that accumulation of senescent cells alters this microenvironment, impairing the response to vaccination. I will test these hypotheses using new mouse models and innovative approaches to human research, in the expectation that the knowledge obtained will promote healthy ageing and uncover novel aspects of GC biology.

Régimen de financiación

ERC-STG - Starting Grant

Coordinador

THE BABRAHAM INSTITUTE
Aportación neta de la UEn
€ 1 499 997,95
Dirección
Babraham hall
CB22 3AT Cambridge
Reino Unido

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Región
East of England East Anglia Cambridgeshire CC
Tipo de actividad
Research Organisations
Enlaces
Coste total
€ 1 499 997,95

Beneficiarios (1)