Adaptive immune cell responses as therapeutic targets in antibody-mediated organ rejection

Kevin Louis; Camila Macedo; Carmen Lefaucheur; Diana Metes

doi:10.1016/j.molmed.2022.01.002

Adaptive immune cell responses as therapeutic targets in antibody-mediated organ rejection

Trends Mol Med. 2022 Mar;28(3):237-250. doi: 10.1016/j.molmed.2022.01.002. Epub 2022 Jan 29.

Authors

Kevin Louis¹, Camila Macedo², Carmen Lefaucheur³, Diana Metes⁴

Affiliations

¹ Kidney Transplant Department, Saint Louis Hospital, Assistance Publique-Hôpitaux de Paris, Paris, France; Human Immunology and Immunopathology, Institut National de la Santé et de la Recherche Médicale UMR 976, Université de Paris, Paris, France.
² Department of Surgery, Thomas E. Starzl Transplantation Institute, University of Pittsburgh Medical Center, Pittsburgh, PA, USA.
³ Kidney Transplant Department, Saint Louis Hospital, Assistance Publique-Hôpitaux de Paris, Paris, France; Paris Translational Research Center for Organ Transplantation, Institut National de la Santé et de la Recherche Médicale UMR 970, Université de Paris, Paris, France.
⁴ Department of Surgery, Thomas E. Starzl Transplantation Institute, University of Pittsburgh Medical Center, Pittsburgh, PA, USA; Department of Immunology, University of Pittsburgh, Pittsburgh, PA, USA. Electronic address: metesdm@upmc.edu.

Abstract

Humoral alloimmunity of organ transplant recipient to donor can lead to antibody-mediated rejection (ABMR), causing thousands of organ transplants to fail each year worldwide. However, the mechanisms of adaptive immune cell responses at the basis of humoral alloimmunity have not been entirely understood. In this review, we discuss how recent investigations have uncovered the key contributions of T follicular helper (T_FH) and B cells and their coordinated actions in driving donor-specific antibody generation and immune progression towards ABMR. We show how recognition of the role of T_FH-B cell interactions may allow the elaboration of improved clinical strategies for immune monitoring and the identification of novel therapeutic targets to tackle ABMR that will ultimately improve organ transplant survival.

Keywords: B cells; T follicular helper cells; alloimmunity; humoral response; organ transplantation.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Review

MeSH terms

Antibodies
Graft Rejection*
Graft Survival
Humans
Immunity, Humoral
Organ Transplantation* / adverse effects

Substances

Antibodies

Abstract

Publication types

MeSH terms

Substances

Grants and funding