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Updated: Aug 8, 2026

Generation of Induced Regulatory T Cells from Primary Human Naïve and Memory T Cells
Published on: April 16, 2012
Identification and functional characterization of human CD4(+)CD25(+) T cells with regulatory properties isolated
H Jonuleit1, E Schmitt, M Stassen
1Department of Dermatology, University of Mainz, D-55101 Mainz, Germany. jonuleit@hautklinik.klinik.uni-mainz.de
Insights
A specific group of human CD4(+)CD25(+) T cells acts as a potent regulatory cell population. These cells suppress conventional T cell expansion without producing key cytokines, highlighting their unique immune function.
Area of Science:
- Immunology
- Cell Biology
Background:
- Peripheral blood contains various T cell subsets with distinct functions.
- Regulatory T cells (Tregs) play a crucial role in maintaining immune homeostasis.
- Understanding human Treg populations is vital for developing immunotherapies.
Purpose of the Study:
- To identify and characterize a novel subpopulation of human peripheral CD4(+)CD25(+) T cells.
- To investigate the suppressive mechanisms and regulatory properties of these cells.
- To determine the reversibility of their anergic state.
Main Methods:
- Flow cytometry to identify cell surface markers (CD45RO, HLA-DR, CTLA-4).
- Cell proliferation assays to assess expansion after stimulation.
- Suppression assays to evaluate impact on conventional T cells.
- Cytokine analysis (IL-2, IL-4, IFN-gamma) at protein and mRNA levels.
- Cell cycle analysis (G1/G0 arrest).
- Reversibility studies using antibodies and cytokines (IL-2, IL-4).
Main Results:
- A distinct CD4(+)CD25(+) T cell subpopulation was identified, expressing CD45RO, HLA-DR, and intracellular CTLA-4.
- These cells did not expand upon stimulation and suppressed conventional T cell expansion via cell contact.
- Activated cells displayed surface CTLA-4 and exhibited G1/G0 cell cycle arrest.
- No production of IL-2, IL-4, or IFN-gamma was detected.
- The anergic state was resistant to blockade of co-stimulatory and inhibitory pathways but partially reversible with IL-2 or IL-4.
Conclusions:
- Human peripheral blood harbors a resident T cell population with significant regulatory capacity.
- This CD4(+)CD25(+) T cell subset functions as a potent suppressor of T cell responses.
- Their unique characteristics and suppressive mechanisms offer insights into immune regulation and potential therapeutic targets.
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)-gamma 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 beta, 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.
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