Follicular T helper cells and humoral reactivity in kidney transplant patients

G. N. de Graav; M. Dieterich; D. A. Hesselink; K. Boer; M. C. Clahsen-van Groningen; 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

doi:10.1111/cei.12576

Follicular T helper cells and humoral reactivity in kidney transplant patients

G. N. de Graav^*, M. Dieterich, D. A. Hesselink, K. Boer, M. C. Clahsen-van Groningen, 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

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

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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.

Original language	English
Pages (from-to)	329-340
Journal	Clinical and Experimental Immunology
Volume	180
Issue number	2
DOIs	https://doi.org/10.1111/cei.12576
Publication status	Published - May 2015

Keywords

donor-specific antibodies
follicular T helper cell
humoral reactivity
kidney transplantation

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10.1111/cei.12576

Cite this

de Graav, G. N., Dieterich, M., Hesselink, D. A., Boer, K., Clahsen-van Groningen, M. C., Kraaijeveld, R., Litjens, N. H. R., Bouamar, R., Vanderlocht, J., Tilanus, M., Houba, I., Boonstra, A., Roelen, D. L., Claas, F. H. J., Betjes, M. G. H., Weimar, W., & Baan, C. C. (2015). Follicular T helper cells and humoral reactivity in kidney transplant patients. Clinical and Experimental Immunology, 180(2), 329-340. https://doi.org/10.1111/cei.12576

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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.",

keywords = "donor-specific antibodies, follicular T helper cell, humoral reactivity, kidney transplantation",

author = "{de Graav}, {G. N.} and M. Dieterich and Hesselink, {D. A.} and K. Boer and {Clahsen-van Groningen}, {M. C.} and R. Kraaijeveld and Litjens, {N. H. R.} and R. Bouamar and J. Vanderlocht and M. Tilanus and I. Houba and A. Boonstra and Roelen, {D. L.} and Claas, {F. H. J.} and Betjes, {M. G. H.} and W. Weimar and Baan, {C. C.}",

year = "2015",

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de Graav, GN, Dieterich, M, Hesselink, DA, Boer, K, Clahsen-van Groningen, MC, Kraaijeveld, R, Litjens, NHR, Bouamar, R, Vanderlocht, J, Tilanus, M, Houba, I, Boonstra, A, Roelen, DL, Claas, FHJ, Betjes, MGH, Weimar, W & Baan, CC 2015, 'Follicular T helper cells and humoral reactivity in kidney transplant patients', Clinical and Experimental Immunology, vol. 180, no. 2, pp. 329-340. https://doi.org/10.1111/cei.12576

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AU - de Graav, G. N.

AU - Dieterich, M.

AU - Hesselink, D. A.

AU - Boer, K.

AU - Clahsen-van Groningen, M. C.

AU - Kraaijeveld, R.

AU - Litjens, N. H. R.

AU - Bouamar, R.

AU - Vanderlocht, J.

AU - Tilanus, M.

AU - Houba, I.

AU - Boonstra, A.

AU - Roelen, D. L.

AU - Claas, F. H. J.

AU - Betjes, M. G. H.

AU - Weimar, W.

AU - Baan, C. C.

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N2 - 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.

AB - 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.

KW - donor-specific antibodies

KW - follicular T helper cell

KW - humoral reactivity

KW - kidney transplantation

U2 - 10.1111/cei.12576

DO - 10.1111/cei.12576

M3 - Article

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VL - 180

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JO - Clinical and Experimental Immunology

JF - Clinical and Experimental Immunology

SN - 0009-9104

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