Work

Innate-like memory T cells rapidly emerge in humans after gene therapy for SCID-X1

Year: 2025

Type: article

Abstract: Virtual memory T cells, possessing features of innate immune cells, represent a developmental continuum between innate and adaptive immunity. Here, we describe the genesis of virtual memory T cells during early human life. A longitudinal analysis of peripheral T cells after gene therapy for X-linked severe combined immunodeficiency (SCID-X1) in infants revealed an early enrichment of innate-like memory CD8 + T cells that expressed NKG2A, innate-associated transcriptional profiles, and a distinct T cell receptor (TCR) repertoire. Genome-wide DNA methylation profiling of the de novo innate-like memory NKG2A + T cell subset confirmed a subset-specific epigenetic signature that included a poised effector response. Furthermore, ex vivo stimulation of NKG2A + T cells with IL-12 and IL-18 resulted in antigen-independent interferon gamma (IFNγ) expression. Collectively, these data indicate that NKG2A + innate-like memory T cells develop early in human life and are epigenetically poised to rapidly elicit effector cytokines in an antigen-independent manner.

Source: Immunity

DOI: 10.1016/j.immuni.2025.07.002

Authors: Anoop Babu Vasandan, Hossam A. Abdelsamed, Shannon K. Boi, Grace Ward, Shanta Alli, Tian Mi, Xin Lan, Xusheng Zhang, Morton J. Cowan, Jennifer M. Puck, Aleksandra Petrovic, David Rawlings, Albert Zhou, Ewelina Mamcarz, Stephen Gottschalk, Caitlin C. Zebley, Ben Youngblood

Institutions: St. Jude Children's Research Hospital, Augusta University, University of Tennessee Health Science Center, University of California, San Francisco, UCSF Benioff Children's Hospital, University of Washington, Seattle Children's Research Institute

Language: English

Topic: T-cell and B-cell Immunology

Subfield: Immunology

Field: Immunology and Microbiology

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: hybrid

Estimated APC paid: $10,400

Funders: Assisi Foundation of Memphis, Alex's Lemonade Stand Foundation for Childhood Cancer, Until There's A Cure Foundation, California Institute of Regenerative Medicine, Israel National Road Safety Authority, American Lebanese Syrian Associated Charities, National Institutes of Health, Stand Up To Cancer, National Heart, Lung, and Blood Institute, National Cancer Institute, National Institute of Allergy and Infectious Diseases

Awards: G1160065765, G1949836847, G204165213, Primary Immune Deficiency Treatment Consortium, G2988707659, G3135729379, G3541808558, G3915808128, G5947087966, Decoding the epigenetic landscape that delineates T cell homeostatic proliferation from uncontrolled growth”, Investigating mechanisms underscoring dichotomous T cell responses between medulloblastoma subgroups, G9000021666, G9000042081, G9000087698, G9000097741

OpenAlex ID: W4412790753

FWCI: 1.178

Cites: 45

Cited by: 4

Related to: 10