[HTML][HTML] The calcineurin inhibitor tacrolimus specifically suppresses human T follicular helper cells

EF Wallin, DL Hill, MA Linterman, KJ Wood - Frontiers in Immunology, 2018 - frontiersin.org
EF Wallin, DL Hill, MA Linterman, KJ Wood
Frontiers in Immunology, 2018frontiersin.org
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 …
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.
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