CD4(+)CD25(+) regulatory T (Treg) cells are crucial mediators of autoimmune tolerance. The factors that regulate Treg cells, however, are largely unknown. Here, we show that deficiency in midkine (MK), a heparin-binding growth factor involved in oncogenesis, inflammation, and tissue repair, attenuated experimental autoimmune encephalomyelitis (EAE) because of an expansion of the Treg cell popul...

BACKGROUND Human regulatory T cells (Treg) offer an attractive adjunctive therapy to reduce current reliance on lifelong, nonspecific immunosuppression after transplantation. Here, we evaluated the ability of ex vivo expanded human Treg to prevent the rejection of islets of Langerhans in a humanized mouse model and examined the mechanisms involved. METHODS We engrafted human pancreatic islets...

INTRODUCTION To evaluate the effect of late initiation of HAART and poor immune reconstitution on the frequency of regulatory T-cells (Treg) in the peripheral blood and gut of HIV-infected patients, we studied Colombian HIV-infected patients who had been on suppressive HAART for at least one year. They had undetectable viremia but were either immunological responders (HIR); (CD4 counts >500 cel...

Evidences are accumulating that CD4⁺ T cells can physiologically mediate antigen specific target cell lysis. By circumventing major histocompatibility complex (MHC)-restrictions through an engineered chimeric antigen receptor (CAR), CD4⁺ T cells lyse defined target cells as efficiently as do CD8⁺ T cells. However, the cytolytic capacity of redirected CD4⁺CD25- T cells, in comparison with CD4⁺CD...

Regulatory T (Treg) cells enforce T cell homeostasis and maintain peripheral T cell tolerance. Here we report a previously unappreciated phenomenon of acute T cell lymphopenia in secondary lymphoid organs and non-lymphoid tissues triggered by Treg cell depletion that precedes the expansion of self-reactive T cells. Lymphopenia affects both neonates and adults indicating a dominant role of Treg ...

Compelling evidence from animal studies has demonstrated that allospecific FoxP3(+)CD4(+) regulatory T (Treg) cells expanded ex vivo can be used as effective therapeutic tools in the treatment of allograft rejection and graft-vs-host disease. Despite the promising results from animal studies, there remain major barriers to developing Treg cell-based immunotherapy in humans. Currently, no effect...

Mucosal administration of Ag conjugated to cholera toxin B subunit (CTB) can efficiently induce peripheral immunologic tolerance, so-called oral tolerance, associated with development of Foxp3(+)CD25(+)CD4(+) regulatory T (Treg) cells. Using an established sublingual tolerization regimen with Ag(OVA)/CTB conjugate, wherein CTB mediates Ag uptake and presentation by most B lymphocytes irrespecti...

The Sle1 locus is a key determinant of lupus susceptibility in the NZM2410 mouse model. Within Sle1, we have previously shown that Sle1a expression enhances activation levels and effector functions of CD4(+) T cells and reduces the size of the CD4(+)CD25(+)Foxp3(+) regulatory T cell subset, leading to the production of autoreactive T cells that provide help to chromatin-specific B cells. In thi...

Defects in regulatory T cells (Treg cells) aggravate multiple sclerosis (MS) after its onset and the absence of Treg cell functions can also exacerbate the course of disease in an animal model of MS. However, autoimmune neuroinflammation in many MS models can be acutely provoked in healthy animals leading to an activation of encephalitogenic T cells despite the induction of immune tolerance in ...

Regulatory T (Treg) cells expressing Foxp3 transcripton factor are essential for immune homeostasis. They arise in the thymus as a separate lineage from conventional CD4(+)Foxp3(-) T (Tconv) cells. Here, we show that the thymic development of Treg cells depends on the expression of their endogenous cognate self-antigen. The formation of these cells was impaired in mice lacking this self-antigen...