An overview of T follicular cells in transplantation: spotlight on their clinical significance

ABSTRACT

Introduction: For late stage organ failure patients, transplantation is the best option to increase life expectancy with a superior quality of life. Unfortunately, after transplantation many patients are at risk of cellular and antibody-mediated rejection (ABMR). The latter is initiated by donor specific antibodies (DSA) which depend on the actions of B cells, T follicular helper (Tfh) cells and T follicular regulatory (Tfr) cells that are present in the germinal center of lymphoid organs.

Areas covered: In this overview paper, we discuss the biology and function of Tfh and Tfr cells in lymphoid tissues, transplanted organs and their circulating counterparts. We report on their relevance to alloimmunity and on the effects of immunosuppressive drugs on these immunocompetent cell populations.

Expert opinion: Growing knowledge about the actions of Tfh and Tfr allows for a better understanding of the immunological mechanisms of ABMR after organ transplantation. This understanding feeds the hypothesis that immunosuppressive drugs targeting the actions of Tfh cells have huge therapeutic potential. This new concept in the treatment of the humoral rejection response will improve graft and patient survival after organ transplantation.

KEYWORDS:

• Antibody mediated rejection
• biomarker
• follicular T cells
• IL-21
• immunosuppression
• transplantation

Article highlights

• B cell-dependent humoral alloimmunity depends on the help of the Tfh cell, a CD4⁺ T helper cell subset. Its counterpart is the Tfr cell, which controls Tfh cell and B cell responses.

• Immunophenotyping and functional analysis of cTfh and Tfr cells in recipients before and after transplantation can help monitor the effects of immunosuppressive therapy on these T cell populations.

• Successfully modulating the immune system via recovering the balance between follicular effector and regulatory cells may promote the induction of allo-tolerance in transplant recipients.

• Most of the conventional immunosuppressive agents used in organ transplantation, and some of the new drugs targeting cell signaling, impact on Tfh cells, although their role in affecting Tfr cells is unclear.

• Further studies on Tfh and Tfr cells in the context of transplantation would offer exciting opportunities to develop novel immunosuppressants for modulating the immune system to minimize humoral rejection and favor transplant tolerance. Targeting the IL-6 and IL-21 pathway are candidates for this development.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This work was supported by the Erasmus MC (mRACE grant 2016) and the National Natural Science Foundation of China (grant No. 81501816, 81871713 and 81571561).