Early-life thymectomy leads to an increase of granzyme-producing γδ T cells in children with congenital heart disease

Alexa Cramer, Tao Yang, Lennart Riemann, Vicente Almeida, Christoph Kammeyer, Yusuf E. Abu, Elisa Gluschke, Svea Kleiner, Ximena León-Lara, Anika Janssen, Alejandro Hofmann, Alexander Horke, Constantin Kaisenberg, Reinhold Förster, Philipp Beerbaum, Martin Boehne and Sarina Ravens ()
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Alexa Cramer: Hannover Medical School
Tao Yang: Hannover Medical School
Lennart Riemann: Hannover Medical School
Vicente Almeida: Hannover Medical School
Christoph Kammeyer: Hannover Medical School
Yusuf E. Abu: Hannover Medical School
Elisa Gluschke: Hannover Medical School
Svea Kleiner: Hannover Medical School
Ximena León-Lara: Hannover Medical School
Anika Janssen: Hannover Medical School
Alejandro Hofmann: Hannover Medical School
Alexander Horke: Transplantation and Vascular Surgery, Hannover Medical School
Constantin Kaisenberg: Gynecology and Reproductive Medicine, Hannover Medical School (MHH)
Reinhold Förster: Hannover Medical School
Philipp Beerbaum: Hannover Medical School
Martin Boehne: Hannover Medical School
Sarina Ravens: Hannover Medical School

Nature Communications, 2024, vol. 15, issue 1, 1-17

Abstract: Abstract Congenital heart disease (CHD) is the most common birth defect in newborns, often requiring cardiac surgery with concomitant thymectomy that is known to increase disease susceptibility later in life. Studies of γδ T cells, which are one of the dominant T cells in the early fetal human thymus, are rare. Here, we provide a comprehensive analysis of the γδ T cell compartment via flow cytometry and next-generation sequencing in children and infants with CHD, who underwent cardiac surgery shortly after birth. A perturbation of the γδ T cell repertoire is evident, and Vδ1 T cell numbers are reduced. However, those cells that are present, do retain cytotoxicity. In contrast, GZMA+CD28+CD161hi innate effector Vγ9Vδ2 T cells are found in higher proportions. TCR-seq identifies an increase in TRDJ3+ γδ T cell clones in children with CHD, but not in a confirmatory group of neonates prior to CHD surgery, which overall points to a persistence of fetal-derived effector γδ T cells in children with CHD.

Date: 2024
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DOI: 10.1038/s41467-024-51673-3

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