Early-life compartmentalization of human T cell differentiation and regulatory function in mucosal and lymphoid tissues

Nat Med. 2016 Jan;22(1):72-7. doi: 10.1038/nm.4008. Epub 2015 Dec 14.

Abstract

It is unclear how the immune response in early life becomes appropriately stimulated to provide protection while also avoiding excessive activation as a result of diverse new antigens. T cells are integral to adaptive immunity; mouse studies indicate that tissue localization of T cell subsets is important for both protective immunity and immunoregulation. In humans, however, the early development and function of T cells in tissues remain unexplored. We present here an analysis of lymphoid and mucosal tissue T cells derived from pediatric organ donors in the first two years of life, as compared to adult organ donors, revealing early compartmentalization of T cell differentiation and regulation. Whereas adult tissues contain a predominance of memory T cells, in pediatric blood and tissues the main subset consists of naive recent thymic emigrants, with effector memory T cells (T(EM)) found only in the lungs and small intestine. Additionally, regulatory T (T(reg)) cells comprise a high proportion (30-40%) of CD4(+) T cells in pediatric tissues but are present at much lower frequencies (1-10%) in adult tissues. Pediatric tissue T(reg) cells suppress endogenous T cell activation, and early T cell functionality is confined to the mucosal sites that have the lowest T(reg):T(EM) cell ratios, which suggests control in situ of immune responses in early life.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Cell Differentiation / immunology*
  • Cytokines / immunology*
  • Female
  • Flow Cytometry
  • Humans
  • Infant
  • Intestinal Mucosa / immunology
  • Intestines / immunology
  • Lung / immunology
  • Lymph Nodes / immunology
  • Lymphoid Tissue / immunology*
  • Male
  • Middle Aged
  • Mucous Membrane / immunology*
  • Respiratory Mucosa / immunology
  • Spleen / immunology
  • T-Lymphocyte Subsets / immunology
  • T-Lymphocytes / immunology*
  • T-Lymphocytes, Regulatory / immunology
  • Thymus Gland / immunology
  • Young Adult

Substances

  • Cytokines