Increased CD40L+PD-1+ follicular helper T cells (Tfh) as a biomarker for predicting calcineurin inhibitor sensitivity against Tfh-mediated B-cell activation/antibody production after kidney transplantation
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- Kenta Iwasaki
- Department of Kidney Disease and Transplant Immunology, Aichi Medical University School of Medicine, Nagakute, Aichi, Japan
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- Nana Kitahata
- Department of Kidney Disease and Transplant Immunology, Aichi Medical University School of Medicine, Nagakute, Aichi, Japan
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- Takahisa Hiramitsu
- Nagoya Daini Red Cross Hospital, Department of Nephrology, 2-9 Myoken-cho, Showa-ku, Nagoya, Japan
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- Takayuki Yamamoto
- Nagoya Daini Red Cross Hospital, Department of Nephrology, 2-9 Myoken-cho, Showa-ku, Nagoya, Japan
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- Takayuki Noda
- Department of Kidney Disease and Transplant Immunology, Aichi Medical University School of Medicine, Nagakute, Aichi, Japan
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- Manabu Okada
- Nagoya Daini Red Cross Hospital, Department of Nephrology, 2-9 Myoken-cho, Showa-ku, Nagoya, Japan
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- Shunji Narumi
- Nagoya Daini Red Cross Hospital, Department of Nephrology, 2-9 Myoken-cho, Showa-ku, Nagoya, Japan
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- Yoshihiko Watarai
- Nagoya Daini Red Cross Hospital, Department of Nephrology, 2-9 Myoken-cho, Showa-ku, Nagoya, Japan
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- Yuko Miwa
- Department of Kidney Disease and Transplant Immunology, Aichi Medical University School of Medicine, Nagakute, Aichi, Japan
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- Kazuharu Uchida
- Department of Kidney Disease and Transplant Immunology, Aichi Medical University School of Medicine, Nagakute, Aichi, Japan
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- Yutaka Matsuoka
- Department of Renal Transplant Surgery, Aichi Medical University School of Medicine, Nagakute, Aichi, Japan
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- Kosei Horimi
- Department of Renal Transplant Surgery, Aichi Medical University School of Medicine, Nagakute, Aichi, Japan
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- Takaaki Kobayashi
- Department of Renal Transplant Surgery, Aichi Medical University School of Medicine, Nagakute, Aichi, Japan
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説明
<jats:title>Abstract</jats:title> <jats:p>It is unclear to what extent the development of follicular helper T cells (Tfh) and de novo donor-specific human leukocyte antigen antibody (DSA) production could be influenced by immunosuppressive agents, particularly calcineurin inhibitor (CNI; cyclosporine or tacrolimus), after kidney transplantation. Here, the effects of immunosuppressive agents on Tfh-mediated B-cell activation and antibody production were investigated. In vitro circulating Tfh (cTfh; memory CD4+CXCR5+)/B-cell (CD19+) co-culture assays revealed that CNI considerably inhibited cTfh-mediated B-cell activation and IgG antibody secretion through the suppression of IL-21 and IL-2. Both IL-21 and CD40L up-regulated IL-2 receptors (CD25) on B cells, and anti-CD25 antibody induced apoptosis of activated B cells, resulting in the inhibition of IgG production. The frequency of cTfh-expressed CD40L and PD-1 was elevated in patients with de novo DSA 1 year after transplantation. The degree of inhibition by CNI was dependent on Staphylococcal enterotoxin B-induced CD40L+PD-1+ cTfh up-regulation level. Our data demonstrate that CD40L+PD-1+cTfh could be a marker to implicate individual difference in CNI sensitivity for Tfh-mediated B-cell activation in kidney transplantation.</jats:p>
収録刊行物
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- International Immunology
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International Immunology 30 (8), 345-355, 2018-06-07
Oxford University Press (OUP)