0000000000295295
AUTHOR
Franz-joseph Schneider
Protection from graft-versus-host disease by HIV-1 envelope protein gp120-mediated activation of human CD4+CD25+ regulatory T cells.
AbstractNaturally occurring CD4+CD25+ regulatory T cells (Tregs) represent a unique T-cell lineage that is endowed with the ability to actively suppress immune responses. Therefore, approaches to modulate Treg function in vivo could provide ways to enhance or reduce immune responses and lead to novel therapies. Here we show that the CD4 binding human immunodeficiency virus-1 envelope glycoprotein gp120 is a useful and potent tool for functional activation of human Tregs in vitro and in vivo. Gp120 activates human Tregs by binding and signaling through CD4. Upon stimulation with gp120, human Tregs accumulate cyclic adenosine monophosphate (cAMP) in their cytosol. Inhibition of endogeneous cA…
Generation of monoclonal antibodies against human regulatory T cells.
Abstract Natural CD4 + CD25 + Foxp3 + regulatory T cells (Tregs) control the activation of the immune system and therefore have become a major area of research in immunology. The generation of monoclonal antibodies against human Tregs offers the possibility to discover novel Treg-specific or Treg-associated surface markers and to identify targets for a therapeutic modulation of Tregs. Here we present a methodology optimized to efficiently induce and select mAb against human Tregs by repeated immunization of mice with Tregs from a single donor and a differential two-step flow cytometry-based hybridoma screening procedure.
Soluble GARP has potent antiinflammatory and immunomodulatory impact on human CD4+ T cells
Glycoprotein A repetitions predominant (GARP) is expressed on the surface of activated human regulatory T cells (Treg) and regulates the bioavailability of transforming growth factor-β (TGF-β). GARP has been assumed to require membrane anchoring. To investigate the function of GARP in more detail, we generated a soluble GARP protein (sGARP) and analyzed its impact on differentiation and activation of human CD4⁺ T cells. We demonstrate that sGARP efficiently represses proliferation and differentiation of naïve CD4⁺ T cells into T effector cells. Exposure to sGARP induces Foxp3, decreases proliferation and represses interleukin (IL)-2 and interferon-γ production, resulting in differentiation …
Large scale preparation of human MHC class II+ integrin beta(1)+ Tregs.
Abstract The human CD4 + CD25 + FoxP3 + regulatory T cell population (Tregs) contains both MHC class II + and MHC class II − cells. MHC class II + Tregs belong to the integrin α 4 β 1 + subpopulation and exclusively execute contact-dependent suppressive activity. Here we present a method optimized for isolation of these MHC class II expressing Tregs from large leukaphereses products using magnetic microbeads that achieves a reproducible purity of more than 90% and enables the use of this small-sized Treg population in pre-clinical application and basic research.