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Cell Mol Immunol. 2017 Jun;14(6):497-510. doi: 10.1038/cmi.2015.101. Epub 2016 Feb 29.

T follicular helper expansion and humoral-mediated rejection are independent of the HVEM/BTLA pathway.

Author information

1
Transplantation Immunobiology Section, Institute of Biomedicine, University of Leon and Castilla and Leon Regional Transplantation Coordination, Leon University Hospital, Leon, Spain.
2
Department of Veterinary Clinical Sciences, University of Santiago de Compostela, Veterinary Faculty, Lugo, Spain.
3
Visceral and Transplantation Surgery, Department of Surgery, University Hospitals of Geneva and Faculty of Medicine, Geneva, Switzerland.

Abstract

The molecular pathways contributing to humoral-mediated allograft rejection are poorly defined. In this study, we assessed the role of the herpesvirus entry mediator/B- and T-lymphocyte attenuator (HVEM/BTLA) signalling pathway in the context of antibody-mediated allograft rejection. An experimental setting was designed to elucidate whether the blockade of HVEM/BTLA interactions could modulate de novo induction of host antidonor-specific antibodies during the course of graft rejection. To test this hypothesis, fully allogeneic major histocompatibility complex-mismatched skin grafts were transplanted onto the right flank of recipient mice that were treated with isotype control, anti-CD40L or modulatory antibodies of the HVEM/BTLA signalling pathway. The frequencies of CD4 T follicular helper (Tfh) cells (B220-, CD4+ CXCR5+ PD-1high), extrafollicular helper cells (B220-, CD4+ CXCR5- PD-1+ and PD-1-) and germinal centre (GC) B cells (B220+Fas+ GL7+) were analysed by flow cytometry in draining and non-draining lymph nodes at day 10 post transplantation during the acute phase of graft rejection. The host antidonor isotype-specific humoral immune response was also assessed. Whereas blockade of the CD40/CD40L pathway was highly effective in preventing the allogeneic humoral immune response, antibody-mediated blockade of the HVEM/BTLA-interacting pathway affected neither the expansion of Tfh cells nor the expansion of GC B cells. Consequently, the course of the host antidonor antibody-mediated response proceeded normally, without detectable evidence of impaired development. In summary, these data indicate that HVEM/BTLA interactions are dispensable for the formation of de novo host antidonor isotype-specific antibodies in transplantation.

PMID:
26924526
PMCID:
PMC5518812
DOI:
10.1038/cmi.2015.101
[Indexed for MEDLINE]
Free PMC Article

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