Follicular T helper cells and humoral reactivity in kidney transplant patients

• DOI: 10.1111/cei.12576
• Publication Date: 2014-12-30T09:13:26Z
• Authors: G N de Graav; M Dieterich; D A Hesselink; K Boer; M C Clahsen-van G...; R Kraaijeveld; N H R Litjens; R Bouamar; J Vanderlocht; M Tilanus; I Houba; A Boonstra; D L Roelen; F H J Claas; M G H Betjes; W Weimar; C C Baan
• Keywords: Adult; Graft Rejection; Immunosuppression Therapy; Male; 0301 basic medicine; B-Lymphocytes; EMC MM-04-39-05; Interleukins; kidney transplantation; EMC MM-04-20-01; T-Lymphocytes, Helper-Inducer; Middle Aged; humoral reactivity; Kidney Transplantation; donor-specific antibodies; Cell Line; Immunity, Humoral; 3. Good health; follicular T helper cell; 03 medical and health sciences; Humans; Female; Immunologic Memory; Aged

SummaryMemory 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 (CD4POSCXCR5POS 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.