Article

Direct Expansion of Functional CD25+ CD4+ Regulatory T Cells by Antigen-processing Dendritic Cells

Laboratory of Cellular Physiology and Immunology, The Rockefeller University, New York, NY 10021, USA.
Journal of Experimental Medicine (Impact Factor: 13.91). 08/2003; 198(2):235-47. DOI: 10.1084/jem.20030422
Source: PubMed

ABSTRACT An important pathway for immune tolerance is provided by thymic-derived CD25+ CD4+ T cells that suppress other CD25- autoimmune disease-inducing T cells. The antigen-presenting cell (APC) requirements for the control of CD25+ CD4+ suppressor T cells remain to be identified, hampering their study in experimental and clinical situations. CD25+ CD4+ T cells are classically anergic, unable to proliferate in response to mitogenic antibodies to the T cell receptor complex. We now find that CD25+ CD4+ T cells can proliferate in the absence of added cytokines in culture and in vivo when stimulated by antigen-loaded dendritic cells (DCs), especially mature DCs. With high doses of DCs in culture, CD25+ CD4+ and CD25- CD4+ populations initially proliferate to a comparable extent. With current methods, one third of the antigen-reactive T cell receptor transgenic T cells enter into cycle for an average of three divisions in 3 d. The expansion of CD25+ CD4+ T cells stops by day 5, in the absence or presence of exogenous interleukin (IL)-2, whereas CD25- CD4+ T cells continue to grow. CD25+ CD4+ T cell growth requires DC-T cell contact and is partially dependent upon the production of small amounts of IL-2 by the T cells and B7 costimulation by the DCs. After antigen-specific expansion, the CD25+ CD4+ T cells retain their known surface features and actively suppress CD25- CD4+ T cell proliferation to splenic APCs. DCs also can expand CD25+ CD4+ T cells in the absence of specific antigen but in the presence of exogenous IL-2. In vivo, both steady state and mature antigen-processing DCs induce proliferation of adoptively transferred CD25+ CD4+ T cells. The capacity to expand CD25+ CD4+ T cells provides DCs with an additional mechanism to regulate autoimmunity and other immune responses.

0 Bookmarks
 · 
117 Views
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Regulatory T cells (Tregs), expressing CD4 and CD25 as well as Foxp3, are known to play a pivotal role in immunoregulatory function in autoimmune diseases, cancers, and graft rejection. Dendritic cells (DCs) are considered the major antigen-presenting cells (APCs) for initiating these T-cell immune responses, of which CD103(+) DCs are derived from precursor human peripheral blood mononuclear cells (PBMCs). The aim of the present study was to evaluate the capacity of these PBMC-derived CD103(+) DCs to promote the differentiation of antigen-specific Tregs.
    Journal of periodontal & implant science 10/2014; 44(5):235-41.
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Dendritic cells (DCs) are professional antigen-presenting cells (APCs) that play a crucial role in both innate and adaptive immune responses. DCs orient the immune responses by modulating the balance between protective immunity to pathogens and tolerance to self-antigens. Staphylococcus aureus (S. aureus) is a common member of human skin microbiota and can cause severe infections with significant morbidity and mortality. Protective immunity to pathogens by DCs is required for clearance of S. aureus. DCs sense the presence of the staphylococcal components using pattern recognition receptors (PRRs) and then orchestrate immune systems to resolve infections. This review summarizes the possible roles of DCs, in particularly their Toll-like receptors (TLRs) in S. aureus infection and strategies by which the pathogen affects activation and function of DCs.
    Journal of Translational Medicine 12/2014; 12(1):358. · 3.99 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Accumulating evidence shows that immunological tolerance induced by Ag administration together with UVB irradiation is dependent on Foxp3(+) CD4(+) regulatory T (Treg) cells. However, the mechanisms by which UVB controls Treg cells in the skin are currently unclear. In this study, we have shown that exposure to UVB induced expansion of Treg cells up to 50-60% of the CD4(+) T cells in the irradiated skin. The Treg cell expansion in the skin lasted for 2 wk after exposure, which contributed to homeostasis of Treg cells in the periphery later. UVB-expanded Treg cells formed clusters with dendritic cells and proliferated in situ. Furthermore, the expanded Treg cells appeared to derive from neuropilin 1(+) thymus-derived Treg (tTreg) cells in the periphery because UVB-expanded Treg cells possessed Treg cell-specific CpG hypomethylation pattern, as seen in tTreg cells. These results collectively indicate that homeostasis of tTreg cells is controlled by UVB exposure in the skin. UVB therapy may be useful for not only inflammatory skin disorders, but also autoimmunity, transplantation, and allergy.
    Journal of immunology (Baltimore, Md. : 1950). 10/2014;

Full-text (3 Sources)

Download
64 Downloads
Available from
May 21, 2014