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Activation of CD4+ T cells results in rapid proliferation and differentiation into effector and regulatory subsets. CD4+ effector T cell (Teff) (Th1 and Th17) and Treg subsets are metabolically distinct, yet the specific metabolic differences that modify T cell populations are uncertain. Here, we evaluated CD4+ T cell populations in murine models and(More)
Foxp3(+) regulatory T cells (Treg cells) are required for immunological homeostasis. One notable distinction between conventional T cells (Tconv cells) and Treg cells is differences in the activity of phosphatidylinositol-3-OH kinase (PI(3)K); only Tconv cells downregulate PTEN, the main negative regulator of PI(3)K, upon activation. Here we found that(More)
Blockade of co-stimulatory signals to T cells is extremely effective for the induction of transplantation tolerance in immunologically naive rodents. However, infections and inflammation compromise the efficacy of co-stimulation blockade regimens for the induction of tolerance, thereby stimulating the rejection of allografts. Previous studies have shown(More)
Viral infections have been associated with the rejection of transplanted allografts in humans and mice, and the induction of tolerance to allogeneic tissues in mice is abrogated by an ongoing viral infection and inhibited in virus-immune mice. One proposed mechanism for this 'heterologous immunity' is the induction of alloreactive T cell responses that(More)
The peripheral naïve T cell pool is comprised of a heterogeneous population of cells at various stages of development, which is a process that begins in the thymus and is completed after a post-thymic maturation phase in the periphery. One hallmark of naïve T cells in secondary lymphoid organs is their unique ability to produce TNF rapidly after activation(More)
The bidirectional interaction between the immune system and whole-body metabolism has been well recognized for many years. Via effects on adipocytes and hepatocytes, immune cells can modulate whole-body metabolism (in metabolic syndromes such as type 2 diabetes and obesity) and, reciprocally, host nutrition and commensal-microbiota-derived metabolites(More)
Foxp3 + regulatory T cells (T regs) are required for immune homeostasis. One notable distinction between conventional T cells (T conv) and T regs is differential phosphatidylinositol 3-kinase (PI3K) activity: only T conv downregulate PTEN, the primary negative regulator of PI3K, upon activation. Here, we show that control of PI3K in T regs is essential for(More)
Transplantation of allogeneic or "nonself" tissues stimulates a robust immune response leading to graft rejection, and therefore, most recipients of allogeneic organ transplants require the lifelong use of immune suppressive agents. Excellent outcomes notwithstanding, contemporary immunosuppressive medications are toxic, are often not taken by patients, and(More)
PURPOSE OF REVIEW To highlight some of the recent developments in the novel field of immunometabolism and the therapeutic potential of the many regulatory components of this immunometabolic network for transplantation. RECENT FINDINGS In response to cytokines, changes in nutrients, and other alterations in the local milieu, immune cells are capable of(More)
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