Identification and Functional Characterization of Human Cd4+Cd25+ T Cells with Regulatory Properties Isolated from Peripheral Blood

TLDR

A subpopulation of peripheral human CD4⁺CD25⁺ T cells expressing CD45RO, HLA‑DR, and intracellular CTLA‑4 does not expand upon stimulation and markedly suppresses conventional T‑cell proliferation in a contact‑dependent manner. Activated CD4⁺CD25⁺ T cells display prolonged surface CTLA‑4 expression, G1/G0 arrest, and lack of IL‑2, IL‑4, or IFN‑γ production; this anergic state is not reversed by anti‑CD28, anti‑CTLA‑4, anti‑TGF‑β, or anti‑IL‑10 antibodies but is partially restored by IL‑2 or IL‑4, confirming a resident regulatory T‑cell population in human blood.

Abstract

A subpopulation of peripheral human CD4+CD25+ T cells that expresses CD45RO, histocompatibility leukocyte antigen DR, and intracellular cytotoxic T lymphocyte–associated antigen (CTLA) 4 does not expand after stimulation and markedly suppresses the expansion of conventional T cells in a contact-dependent manner. After activation, CD4+CD25+ T cells express CTLA-4 on the surface detectable for several weeks. These cells show a G1/G0 cell cycle arrest and no production of interleukin (IL)-2, IL-4, or interferon (IFN)-γ on either protein or mRNA levels. The anergic state of CD4+CD25+ T cells is not reversible by the addition of anti-CD28, anti–CTLA-4, anti–transforming growth factor β, or anti–IL-10 antibody. However, the refractory state of CD4+CD25+ T cells was partially reversible by the addition of IL-2 or IL-4. These data demonstrate that human blood contains a resident T cell population with potent regulatory properties.