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Updated: Oct 10, 2025

Isolation and Ex Vivo Culture of Vδ1+CD4+γδ T Cells, an Extrathymic αβT-cell Progenitor
Published on: December 7, 2015
Early-life imprinting of unconventional T cells and tissue homeostasis
Michael G Constantinides1, Yasmine Belkaid1,2
1Metaorganism Immunity Section, Laboratory of Immune System Biology, National Institute of Allergy and Infectious Diseases, Bethesda, MD 20892, USA.
Unconventional T cells—including invariant natural killer T (iNKT) cells, mucosal-associated invariant T (MAIT) cells, and defined subsets of γδ T cells—are restricted by monomorphic major histocompatibility complex class Ib (MHC-Ib) molecules and seed tissues during development. Early-life instructive signals, including those derived from the microbiota, establish homeostatic set points for unconventional T cells, a phenomenon that has lifelong consequences for the regulation of tissue immunity, inflammation, and repair. Unconventional T cells compete for niches within tissues, and recent evidence supports the idea that the fundamental role of these cells in tissue physiology may result from their action as a network with overlapping and potentially synergistic functions, rather than as individual subsets.
Unconventional T cells—including invariant natural killer T (iNKT) cells, mucosal-associated invariant T (MAIT) cells, and defined subsets of γδ T cells—are restricted by monomorphic major histocompatibility complex class Ib (MHC-Ib) molecules and seed tissues during development. Early-life instructive signals, including those derived from the microbiota, establish homeostatic set points for unconventional T cells, a phenomenon that has lifelong consequences for the regulation of tissue immunity, inflammation, and repair. Unconventional T cells compete for niches within tissues, and recent evidence supports the idea that the fundamental role of these cells in tissue physiology may result from their action as a network with overlapping and potentially synergistic functions, rather than as individual subsets.
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