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The calcineurin inhibitor tacrolimus specifically suppresses human T follicular helper cells

Abstract:
Background: T follicular helper (Tfh) cells are key players in the production of antibody-producing B cells via the germinal center reaction. Therapeutic strategies targeting Tfh cells are important where antibody formation is implicated in disease, such as transplant rejection and autoimmune diseases. We investigated the impact of the immunosuppressive agent tacrolimus on human Tfh cell differentiation and function in transplant recipients. Methods: Paired blood and lymph node (LN) samples were obtained from 61 transplant recipients immediately prior to organ implantation. Living-donor recipients received a week of tacrolimus prior to kidney transplantation. Deceased-donor recipients served as controls, as tacrolimus was not administered until after the transplant operation. Flow cytometry was used to compare LN and circulating cell subsets. Results: The calcineurin inhibitor (CNIs) tacrolimus specifically suppresses both LN Tfh cells and circulating Tfh cells, but not their regulatory counterparts or other CD4 T cell subsets. Conclusion: Our findings suggest that CNIs may have a more important role in the prevention of antibody formation than previously understood and, therefore, have potential for antibody-associated conditions in which aberrant Tfh function has been implicated in disease.
Publication status:
Published
Peer review status:
Peer reviewed

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Publisher copy:
10.3389/fimmu.2018.01184

Authors


More by this author
Institution:
University of Oxford
Division:
Medical Sciences Division
Department:
Surgical Sciences
Role:
Author
More by this author
Institution:
University of Oxford
Division:
MSD
Department:
Surgical Sciences
Oxford college:
Green Templeton College
Role:
Author


Publisher:
Frontiers Media
Journal:
Frontiers in Immunology More from this journal
Volume:
9
Issue:
MAY
Article number:
1184
Publication date:
2018-05-31
Acceptance date:
2018-05-14
DOI:
ISSN:
1664-3224
Pmid:
29904381


Language:
English
Keywords:
Pubs id:
pubs:856584
UUID:
uuid:4af2a172-3a11-4438-b75a-712c519a8a91
Local pid:
pubs:856584
Source identifiers:
856584
Deposit date:
2018-08-14

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