title: Follicular T helper cells and humoral reactivity in kidney transplant patients.
abstract: Memory B cells play a pivotal role in alloreactivity in kidney transplantation. Follicular T helper (Tfh) cells play an important role in the differentiation of B cells into immunoglobulin-producing plasmablasts [through interleukin (IL)-21]. It is unclear to what extent this T cell subset regulates humoral alloreactivity in kidney transplant patients, therefore we investigated the absolute numbers and function of peripheral Tfh cells (CD4(POS) CXCR5(POS) T cells) in patients before and after transplantation. In addition, we studied their relationship with the presence of donor-specific anti-human leucocyte antigen (HLA) antibodies (DSA), and the presence of Tfh cells in rejection biopsies. After transplantation peripheral Tfh cell numbers remained stable, while their IL-21-producing capacity decreased under immunosuppression. When isolated after transplantation, peripheral Tfh cells still had the capacity to induce B cell differentiation and immunoglobulin production, which could be inhibited by an IL-21-receptor-antagonist. After transplantation the quantity of Tfh cells was the highest in patients with pre-existent DSA. In kidney biopsies taken during rejection, Tfh cells co-localized with B cells and immunoglobulins in follicular-like structures. Our data on Tfh cells in kidney transplantation demonstrate that Tfh cells may mediate humoral alloreactivity, which is also seen in the immunosuppressed milieu.
authors.affiliation: Department of Internal Medicine, Section Transplantation and Nephrology, Erasmus MC, University Medical Center, Rotterdam, the Netherlands.
authors.forename: G N
authors.initials: GN
authors.lastname: de Graav
authors.forename: M
authors.initials: M
authors.lastname: Dieterich
authors.forename: D A
authors.initials: DA
authors.lastname: Hesselink
authors.forename: K
authors.initials: K
authors.lastname: Boer
authors.forename: M C
authors.initials: MC
authors.lastname: Clahsen-van Groningen
authors.forename: R
authors.initials: R
authors.lastname: Kraaijeveld
authors.forename: N H R
authors.initials: NH
authors.lastname: Litjens
authors.forename: R
authors.initials: R
authors.lastname: Bouamar
authors.forename: J
authors.initials: J
authors.lastname: Vanderlocht
authors.forename: M
authors.initials: M
authors.lastname: Tilanus
authors.forename: I
authors.initials: I
authors.lastname: Houba
authors.forename: A
authors.initials: A
authors.lastname: Boonstra
authors.forename: D L
authors.initials: DL
authors.lastname: Roelen
authors.forename: F H J
authors.initials: FH
authors.lastname: Claas
authors.forename: M G H
authors.initials: MG
authors.lastname: Betjes
authors.forename: W
authors.initials: W
authors.lastname: Weimar
authors.forename: C C
authors.initials: CC
authors.lastname: Baan
mesh_terms: D000328:Adult; D000368:Aged; D001402:B-Lymphocytes / Q000276:immunology* / Q000502:physiology; D002460:Cell Line; D005260:Female; D006084:Graft Rejection / Q000276:immunology* / Q000473:pathology / Q000517:prevention & control; D006801:Humans; D056724:Immunity, Humoral; D007156:Immunologic Memory; D007165:Immunosuppression Therapy / Q000379:methods; D007378:Interleukins / Q000276:immunology; D016030:Kidney Transplantation; D008297:Male; D008875:Middle Aged; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology* / Q000473:pathology; D000098546:Interleukin-21
chemical_list: D007378:Interleukins; D000098546:Interleukin-21
keywords: donor-specific antibodies; follicular T helper cell; humoral reactivity; kidney transplantation