The Calcineurin Inhibitor Tacrolimus Specifically Suppresses Human T Follicular Helper Cells

Front Immunol. 2018 May 31;9:1184. doi: 10.3389/fimmu.2018.01184. eCollection 2018.

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.

Keywords: T follicular helper cells; T follicular regulatory cells; germinal centers; immunosuppression; transplantation immunology.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Antibody Formation
  • B-Lymphocytes
  • Calcineurin Inhibitors
  • Cell Differentiation
  • Cytokines / metabolism
  • Female
  • Germinal Center
  • Graft Rejection / immunology*
  • Humans
  • Immunosuppressive Agents
  • Kidney Transplantation*
  • Lymphocyte Activation
  • Male
  • Middle Aged
  • T-Lymphocytes, Helper-Inducer
  • T-Lymphocytes, Regulatory / immunology*
  • Tacrolimus
  • Transplant Recipients

Substances

  • Calcineurin Inhibitors
  • Cytokines
  • Immunosuppressive Agents
  • Tacrolimus