Residual Activatability of Circulating Tfh17 Predicts Humoral Response to Thymodependent Antigens in Patients on Therapeutic Immunosuppression

Frontiers in Immunology
Suzan DahdalOlivier Thaunat

Abstract

The generation of antibodies against protein antigens (such as donor-specific HLA molecules) requires that T follicular helper cells (Tfh) provide help to B cells. Immunosuppressive (IS) armamentarium prevents T cell activation, yet a significant proportion of renal transplant patients develop donor-specific antibodies (DSA), which suggests that IS drugs do not efficiently block T follicular helper cells. To test this hypothesis, the number of circulating Tfh, their polarization profile, and ability to up-regulate (i) the co-stimulatory molecules CD40L and ICOS, and (ii) the activation marker CD25, following in vitro stimulation in presence of IS drugs, were compared between 36 renal transplant patients (6-72 months post transplantation) and nine healthy controls. IS drugs reduced the number of Tfh1 and 2 but had little impact on Tfh17, which was the dominant subset in transplant patients. Although, IS drugs decreased activation-induced expression of co-stimulatory molecules by Tfh, the impact was highly variable between individuals. Furthermore, 20% of transplant patients displayed normal expression of CD25 on Tfh following in vitro stimulation (i.e., "residual activatability"). To test whether residual activatability of Tfh c...Continue Reading

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Citations

Aug 20, 2019·HLA : Immune Response Genetics·Nicole M van BesouwCarla C Baan
Nov 14, 2019·Expert Review of Clinical Immunology·Qian NiuCarla C Baan
Apr 1, 2021·Transplant International : Official Journal of the European Society for Organ Transplantation·Oriol BestardOlivier Thaunat

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BETA
flow cytometry

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FlowJo®

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