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Circulating T follicular helper cells are a biomarker of humoral alloreactivity and predict donor‐specific antibody formation after transplantation
Author(s) -
La Muraglia Glenn Michael,
Wagener Maylene E.,
Ford Mandy L.,
Badell Idelberto Raul
Publication year - 2020
Publication title -
american journal of transplantation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.89
H-Index - 188
eISSN - 1600-6143
pISSN - 1600-6135
DOI - 10.1111/ajt.15517
Subject(s) - germinal center , immunology , antibody , biomarker , transplantation , medicine , cxcr5 , lymph node , b cell , biology , biochemistry
Donor‐specific antibodies ( DSA s) contribute to renal allograft loss. However, biomarkers to guide clinical management of DSA posttransplant or detect humoral alloimmune responses before alloantibodies develop are not available. Circulating T follicular helper ( cT fh) cells are CD 4 + CXCR 5 + Tfh‐like cells in the blood that have been associated with alloantibodies in transplant recipients, but whether they precede antibody formation for their evaluation as a predictive biomarker in transplant is unknown. To evaluate the ability of cT fh cells to predict DSA , we used murine transplant models to determine the temporal relationship between cT fh cells, germinal center formation, and DSA development. We observed that donor‐reactive CD 4 + CXCR 5 + cT fh cells expand after allotransplant. These cT fh cells were equivalent to graft‐draining lymph node‐derived Tfh cells in their ability to provide B cell help for antibody production. cT fh cell expansion and differentiation into ICOS + PD ‐1 + cells temporally correlated with germinal center alloreactivity and preceded the generation of DSA s in instances of modified and unmodified alloantibody formation. Importantly, delayed costimulation blockade initiated after the detection of ICOS + PD ‐1 + cT fh cells prevented DSA s. These findings suggest that cT fh cells could serve as a biomarker for humoral alloreactivity before the detection of alloantibodies and inform therapeutic approaches to prevent DSAs.