Granzyme A-producing T helper cells are critical for acute graft-versus-host disease.
JCI Insight
; 5(18)2020 09 17.
Article
em En
| MEDLINE
| ID: mdl-32809971
ABSTRACT
Acute graft-versus-host disease (aGVHD) can occur after hematopoietic cell transplant in patients undergoing treatment for hematological malignancies or inborn errors. Although CD4+ T helper (Th) cells play a major role in aGVHD, the mechanisms by which they contribute, particularly within the intestines, have remained elusive. We have identified a potentially novel subset of Th cells that accumulated in the intestines and produced the serine protease granzyme A (GrA). GrA+ Th cells were distinct from other Th lineages and exhibited a noncytolytic phenotype. In vitro, GrA+ Th cells differentiated in the presence of IL-4, IL-6, and IL-21 and were transcriptionally unique from cells cultured with either IL-4 or the IL-6/IL-21 combination alone. In vivo, both STAT3 and STAT6 were required for GrA+ Th cell differentiation and played roles in maintenance of the lineage identity. Importantly, GrA+ Th cells promoted aGVHD-associated morbidity and mortality and contributed to crypt destruction within intestines but were not required for the beneficial graft-versus-leukemia effect. Our data indicate that GrA+ Th cells represent a distinct Th subset and are critical mediators of aGVHD.
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Base de dados:
MEDLINE
Assunto principal:
Ativação Linfocitária
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Linfócitos T Auxiliares-Indutores
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Transplante de Células-Tronco Hematopoéticas
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Efeito Enxerto vs Leucemia
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Granzimas
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Doença Enxerto-Hospedeiro
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Intestinos
Idioma:
En
Ano de publicação:
2020
Tipo de documento:
Article