Active Infection & Immunity Cancer

(Lost-Tfh) Lost in space: How spatial dysregulation of T follicular helper cells impairs vaccine responses in ageing

In plain English

AI plain-English summary

As we age, key immune cells called T follicular helpers fail to reach the right location in lymph nodes after a vaccination, leaving the response disorganised. This matters because vaccines work less well in older people, and we do not fully understand why. The researchers have identified a specific spatial problem: these helper cells get “lost in space” and do not rendezvous with the other cells they need to instruct. Without that physical meeting, the immune system cannot produce strong, long-lasting antibodies. The project will map exactly where the cells go wrong and what knock-on effects this has for the rest of the immune response. This is fundamental science. It will not produce a new vaccine or drug directly. But understanding the precise cellular geography of a failed immune response could eventually guide the design of vaccines that physically steer helper cells to the correct location. Similar discoveries about immune cell movement have previously led to improved vaccine adjuvants and cancer immunotherapies. The immediate impact will be a clearer map of what breaks down in the ageing immune system.

View original technical description
A successful response to vaccination requires the cells of the immune system to get together at the right place, and at the right time. We have identified that in older bodies a particular type of white blood cell, helper T cells, does not get to the right place after immunisation. This proposal aims to determine why, and to identify what the consequences are of these lost-helpers for the immune response to vaccination and for the other cell types that they would normally interact with.

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Researchers

Michelle Linterman (Principal Investigator)

Related Research

Grants with similar aims, by meaning.

ToWards Immunisations that Last: the Immunology and Gerontology of Helper T cells
Boosting vaccine responses in older persons
Impaired selection of germinal centre B cells in ageing diminishes the quality of antibody mediated immunity upon vaccination
Dynamics of human T cell memory in blood and secondary lymphoid tissue in shaping vaccine induced immunity in ageing
Lymph node remodelling for optimal vaccine responses

Original classification

Research Grant

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