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Br J Haematol. 2019 Jun 20. doi: 10.1111/bjh.16053. [Epub ahead of print]

T-cell receptor sequencing demonstrates persistence of virus-specific T cells after antiviral immunotherapy.

Author information

1
Division of Allergy & Immunology, Children's National Health System, Washington, DC, USA.
2
Center for Cancer and Immunology Research, Children's National Health System, Washington, DC, USA.
3
Vaccine Research Center, National Institute of Allergy and Infectious Disease, Bethesda, MD, USA.
4
Clinical and Translational Sciences Institute, Children's National Health System, Washington, DC, USA.
5
Division of Blood and Marrow Transplantation, Children's National Health System, Washington, DC, USA.
6
Division of Allergy & Immunology, Children's Hospital of Philadelphia, Philadelphia, PA, USA.
7
Division of Blood and Marrow Transplantation, Johns Hopkins Hospital, Baltimore, MD, USA.
8
GW Cancer Center, George Washington University, Washington, DC, USA.
9
Center for Cell and Gene Therapy, Baylor College of Medicine, Houston Methodist Hospital and Texas Children's Hospital, Houston, TX, USA.

Abstract

Viral infections are a serious cause of morbidity and mortality following haematopoietic stem cell transplantation (HSCT). Adoptive cellular therapy with virus-specific T cells (VSTs) has been successful in preventing or treating targeted viruses in prior studies, but the composition of ex vivo expanded VST and the critical cell populations that mediate antiviral activity in vivo are not well defined. We utilized deep sequencing of the T-cell receptor beta chain (TCRB) in order to classify and track VST populations in 12 patients who received VSTs following HSCT to prevent or treat viral infections. TCRB sequencing was performed on sorted VST products and patient peripheral blood mononuclear cells samples. TCRB diversity was gauged using the Shannon entropy index, and repertoire similarity determined using the Morisita-Horn index. Similarity indices reflected an early change in TCRB diversity in eight patients, and TCRB clonotypes corresponding to targeted viral epitopes expanded in eight patients. TCRB repertoire diversity increased in nine patients, and correlated with cytomegalovirus (CMV) viral load following VST infusion (P = 0·0071). These findings demonstrate that allogeneic VSTs can be tracked via TCRB sequencing, and suggests that T-cell receptor repertoire diversity may be critical for the control of CMV reactivation after HSCT.

KEYWORDS:

T-lymphocyte; adoptive immunotherapy; haematopoietic stem cell transplantation; viral infection

PMID:
31219185
DOI:
10.1111/bjh.16053

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