A rare opportunity to use both blood and tissue samples from human transplant recipients has allowed immunology researchers at the Babraham Institute to pinpoint how an immunosuppressive drug works to prevent the production of antibodies against the transplanted tissue. This understanding, gained through working together with transplant research immunologists in Oxford, may lead to improved ways of identifying transplant recipients at risk of rejection and treating autoimmune disease.
As described in a paper published today, the researchers assessed the effect of treatment with an immunosuppressive drug called tacrolimus on a type of immune cell called T follicular helper cells (Tfh). These cells are central to the production of antibodies and are a target of therapeutic strategies to manage unwanted destructive antibodies, for example in auto-immune diseases or in organ transplantation.
Blood and lymph nodes samples were analysed from 61 kidney transplant recipients, some of which had been treated with tacrolimus before the transplant operation. Using both blood and lymph node samples allowed the comparison of circulating immune cells with their counterparts residing in the lymph nodes.
The researchers identified that tacrolimus specifically reduced the number of both circulating Tfh cells and Tfh cells found in the lymph nodes. Confirming this is important for monitoring donor recipients post-transplant which can only be done using blood samples. Reduced numbers of Tfh cells overall would be expected to correlate with suppressed organ rejection whereas a high Tfh cell number would be indicative of an immune response potentially causing organ damage.
Babraham Institute group leader and joint senior author, Dr Michelle Linterman, said: “Now we have identified tacrolimus as a drug that can inhibit T follicular helper cells and reduce the formation of antibodies, it suggests we can use this drug as a way to treat conditions where the action of T follicular helper cells is an underlying cause of disease.”
These findings identify the diagnostic relevance of using Tfh cells as a biomarker to assess the immunosuppression status of organ recipients. It points to developments in patient care based upon the status of their immune system, giving a more accurate picture than allowed by current methods monitoring the levels of immunosuppressive drugs in the body.
Wallin, E.F., Hill, D.L., Linterman, M.A., Wood, K.J. The calcineurin inhibitor tacrolimus specifically suppresses human Tfh cells, limiting antibody production. Frontiers in Immunology 2018
The research undertaken at the Babraham Institute by Michelle Linterman and Danika Hill was supported by the strategic funding to the Institute from the Bioscience and Biotechnology Research Council. The work in this paper was also supported by a Kidney Research UK/MRC Clinical Fellowship to Elizabeth Wallin and grants from the European Commission FP7 programme – The ONE Study and BioDRIM.
Dr Louisa Wood, Communications Manager, firstname.lastname@example.org
Tfh cells (green) within a germinal centre. Germinal centres are specialised sites of immune cell proliferation found in lymph nodes and the spleen. Credit: Ine Vanderleyden, Babraham Institute
Affiliated authors (in author order)
Danika Hill – Lymphocycte Signalling programme, Babraham InstituteMichelle Linterman – Group leader, Immunology programme, Babraham Institute
Blog post: Transplanting science - bringing together basic biology and clinical care
About the Babraham Institute
The Babraham Institute receives strategic funding from the Biotechnology and Biological Sciences Research Council (BBSRC) through an Institute Core Capability Grant to undertake world-class life sciences research. Its goal is to generate new knowledge of biological mechanisms underpinning ageing, development and the maintenance of health. Research focuses on signalling, gene regulation and the impact of epigenetic regulation at different stages of life. By determining how the body reacts to dietary and environmental stimuli and manages microbial and viral interactions, we aim to improve wellbeing and support healthier ageing.
31 May 2018