A Human Memory T Cell Subset With Stem Cell-Like Properties

Nat Med. 2011 Sep 18;17(10):1290-7. doi: 10.1038/nm.2446.

Abstract

Immunological memory is thought to depend on a stem cell-like, self-renewing population of lymphocytes capable of differentiating into effector cells in response to antigen re-exposure. Here we describe a long-lived human memory T cell population that has an enhanced capacity for self-renewal and a multipotent ability to derive central memory, effector memory and effector T cells. These cells, specific to multiple viral and self-tumor antigens, were found within a CD45RO(-), CCR7(+), CD45RA(+), CD62L(+), CD27(+), CD28(+) and IL-7Rα(+) T cell compartment characteristic of naive T cells. However, they expressed large amounts of CD95, IL-2Rβ, CXCR3, and LFA-1, and showed numerous functional attributes distinctive of memory cells. Compared with known memory populations, these lymphocytes had increased proliferative capacity and more efficiently reconstituted immunodeficient hosts, and they mediated superior antitumor responses in a humanized mouse model. The identification of a human stem cell-like memory T cell population is of direct relevance to the design of vaccines and T cell therapies.

Publication types

  • Research Support, N.I.H., Intramural

MeSH terms

  • Analysis of Variance
  • Animals
  • CD28 Antigens / metabolism
  • Cell Proliferation*
  • Flow Cytometry
  • Gene Expression Profiling
  • Humans
  • Immunologic Memory*
  • L-Selectin / metabolism
  • Leukocyte Common Antigens / metabolism
  • Mice
  • Receptors, CCR7 / metabolism
  • Receptors, Interleukin-7 / metabolism
  • T-Lymphocyte Subsets / immunology*
  • T-Lymphocyte Subsets / metabolism
  • T-Lymphocytes / cytology*
  • T-Lymphocytes / immunology*
  • T-Lymphocytes / metabolism
  • Tumor Necrosis Factor Receptor Superfamily, Member 7 / metabolism

Substances

  • CCR7 protein, human
  • CD28 Antigens
  • Receptors, CCR7
  • Receptors, Interleukin-7
  • Tumor Necrosis Factor Receptor Superfamily, Member 7
  • interleukin-7 receptor, alpha chain
  • L-Selectin
  • Leukocyte Common Antigens

Associated data

  • GEO/GSE23321