- Paper Report
- Open Access
Regulatory T cells in human blood
- Ranjeny Thomas1
© Biomed Central Ltd 2001
- Received: 2 August 2001
- Accepted: 3 September 2001
- Published: 3 September 2001
- regulatory T cells
Three papers in the same issue of J Exp Med and one in J Immunol report the identification and characterization of human peripheral blood (PB) CD4+CD25+ regulatory T cells (see Additional information [1-4]). Subsets of CD4+ and CD8+ T cells, as well as ?d T cells and natural killer T cells, have previously been shown to have regulatory properties. Thus, these cells are broadly known as Treg (see Additional information ). Specifically, human and murine CD4+ T cells with regulatory function have previously been generated in vitro in the presence of either immature dendritic cells (DCs) or monocytes in the presence of IL-10 (called "Tr1 cells"; see Additional information [6,7]). These CD4+ cells typically secrete large amounts of IL-10, low levels of IFN? and no IL-4/5.
Purified CD4+CD25+ cells were predominantly of the CD45RO+ HLA-DR+ memory phenotype. Some constitutively expressed cytotoxic T lymphocyte-associated antigens-4. They expressed CD69 and CD40L upon activation, but proliferated poorly, made no IL-2, IL-4 or IFN? mRNA, and secreted little cytokine in response to mature DC. T-cell proliferation could be improved by incubation with IL-4 and IL-2. CD4+CD25+ T cells suppressed CD4+ T-cell proliferation and IFN? production in the presence of DCs, in a cell-contact-dependent manner. Either cognate interactions with antigen presenting cells (APCs), or ligation of CD3 could induce antigen-nonspecific suppression by this subset. CD4+CD25+ T cells could be expanded in vitro by incubation with anti-CD3 antibodies and cytokines.
flow cytometry, MLR, cytokine production
Jonuleit H, Schmitt E, Schuler G, Knop J, Enk AH: Induction of interleukin 10-producing, nonproliferating CD4+ T cells with regulatory properties by repetitive stimulation with allogeneic immature human dendritic cells. J Exp Med 2000, 192:1213-1222.
Levings MK, Sangregorio R, Roncarolo MG: Human CD25+CD4+ T regulatory cells suppress naive and memory T cell proliferation and can be expanded in vitro without loss of function. J Exp Med 2001, 193:1295-1302.
Dieckmann D, Plottner H, Berchtold S, Berger T, Schuler G: Ex vivo isolation and characterization of CD4+CD25+ T cells with regulatory properties from human blood. J Exp Med 2001, 193:1303-1310.
Baecher-Allan C, Brown JA, Freeman GJ, Hafler DA: CD4+CD25high regulatory cells in human peripheral blood. J Immunol 2001, 167:1245-1253.
Roncarolo MG, Levings MK: The role of different subsets of T regulatory cells in controlling autoimmunity. Curr Opin Immunol 2000, 12:676-683.
Groux H, O'Garra A, Bigler M, Rouleau M, Antonenko S, de Vries JE, Roncarolo MG: A CD4+ T-cell subset inhibits antigen-specific T-cell responses and prevents colitis. Nature 1997, 389:737-742.
Powrie F, Correa-Oliveira R, MauzeS, Coffman RL: Regulatory interactions between CD45RBhigh and CD45RBlow CD4+ T cells are important for the balance between protective and pathogenic cell-mediated immunity. J Exp Med 1994, 179:589-600.
Thomas R, McIlraith M, Davis LS, Lipsky PE: Rheumatoid synovium is enriched in CD45RBdim mature memory T cells that are potent helpers for B cell differentiation. Arthritis Rheum 1992, 35:1455-1465.