Showing papers by "Abul K. Abbas published in 2007"

Interleukin-2 enhances CD4+ T cell memory by promoting the generation of IL-7Rα–expressing cells

Abstract: The common γ chain cytokines interleukin (IL)-2 and IL-7 are important regulators of T cell homeostasis. Although IL-2 is implicated in the acute phase of the T cell response, IL-7 is important for memory T cell survival. We asked whether regulated responsiveness to these growth factors is determined by temporal expression of the cytokine-specific IL-2 receptor (R) α and IL-7Rα chains. We demonstrate that IL-2Rα is expressed early after priming in T cell receptor–transgenic CD4+ T cells, whereas IL-7Rα expression is lost. In the later stage of the response, IL-7Rα is reexpressed while IL-2Rα expression is silenced. This reciprocal pattern of IL-2Rα/IL-7Rα expression is disturbed when CD4+ T cells are primed in the absence of IL-2 signals. Primed IL-2−/− or CD25−/− (IL-2Rα−/−) CD4+ T cells, despite showing normal induction of activation markers and cell division, fail to reexpress IL-7Rα late in the response. Because the generation of CD4+ memory T cells is dependent on IL-7–IL-7Rα interactions, primed IL-2−/− or CD25−/− CD4+ T cells develop poorly into long-lived memory cells. Retrovirus-mediated expression of IL-7Rα in IL-2−/− T cells restores their capacity for long-term survival. These results identify IL-2 as a factor regulating IL-7Rα expression and, consequently, memory T cell homeostasis in vivo.

Comprar Cellular and Molecular Immunology | Shiv Pillai | 9781416031222 | Saunders

Abstract: Tienda online donde Comprar Cellular and Molecular Immunology al precio 63,83 € de Shiv Pillai | Andrew H. Lichtman | Abul K. Abbas, tienda de Libros de Medicina, Libros de Alergologia e Inmunologia - Inmunologia

Role of T cells in a murine model of Escherichia coli sepsis

Abstract: To study the role of T cells in gram-negative sepsis, we developed a mouse model in which i.v. injection of Escherichia coli results in severe systemic illness, with high mortality rates after day 5. A large proportion of both CD4(+) and CD8(+) T cells are activated within 1 day after infection, as evidenced by up-regulation of CD69 and down-regulation of CD62L. Even more surprisingly, T cell-deficient mice exhibit markedly decreased disease severity compared to WT mice, indicating a pathogenic role of T cells. Mice lacking IFN-gamma also show diminished disease, and exhibit reduced T cell activation. Therefore, the pathogenic role of T cells may be mediated by IFN-gamma. Both T cell- and IFN-gamma-deficient mice have reduced serum IL-6 levels compared to WT mice, suggesting that T cells may stimulate innate immune responses, resulting in enhancement of disease. These data indicate an important role for T cells in a mouse model of E. coli sepsis, and reveal an unexpected early and pathogenic T cell response to this bacterial infection.

Targeting T Cell-Specific Costimulators and Growth Factors in a Model of Autoimmune Hemolytic Anemia

Abstract: Although it is established that failure of regulatory mechanisms underlies many autoimmune diseases, the stimuli that activate autoreactive lymphocytes remain poorly understood. Defining these stimuli will lead to therapeutic strategies for autoimmune diseases. IL-2-deficient mice develop spontaneous autoimmunity, because of a deficiency of regulatory T cells, and on the BALB/c background, they rapidly die from autoimmune hemolytic anemia. To define the importance of costimulatory pathways in various components of this autoimmune disorder, we first intercrossed IL-2-deficient mice with mice lacking CD28 or CD40L. Elimination of CD28 reduced the activation of autoreactive T cells and lymphoproliferation as well as production of autoantibodies, whereas elimination of CD40L reduced autoantibody production without affecting T cell expansion and accumulation. To examine the role of IL-7, we blocked IL-7R signaling with neutralizing Abs. This treatment inhibited the production of autoantibodies and the development of autoimmune hemolytic anemia. Together, these data indicate that specific costimulatory and cytokine signals are critical for the spontaneous autoantibody-mediated disease that develops in IL-2-deficient mice.

Constitutive Expression of B7-1 on B Cells Uncovers Autoimmunity toward the B Cell Compartment in the Nonobese Diabetic Mouse

Abstract: The NOD mouse is an invaluable model for the study of autoimmune diabetes. Furthermore, although less appreciated, NOD mice are susceptible to other autoimmune diseases that can be differentially manifested by altering the balance of T cell costimulatory pathways. In this study, we show that constitutively expressing B7-1 on B cells (NOD-B7-1B-transgenic mice) resulted in reduced insulitis and completely protected NOD mice from developing diabetes. Furthermore, B7-1 expression led to a dramatic reduction of the B cell compartment due to a selective deletion of follicular B cells in the spleen, whereas marginal zone B cells were largely unaffected. B cell depletion was dependent on B cell specificity, mediated by CD8 + T cells, and occurred exclusively in the autoimmune-prone NOD background. Our results suggest that B cell deletion was a consequence of the specific activation of autoreactive T cells directed at peripheral self Ags presented by maturing B cells that expressed B7-1 costimulatory molecules. This study underscores the importance of B7 costimulatory molecules in controlling the amplitude and target of autoimmunity in genetically prone individuals and has important implications in the use of costimulatory pathway antagonists in the treatment of human autoimmune diseases.

Comprar Robbins Basic Pathology | Vinay Kumar | 9781416029731 | Saunders

Abstract: Tienda online donde Comprar Robbins Basic Pathology al precio 69,81 € de Vinay Kumar | Abul K. Abbas | Nelson Fausto | Richard Mitchell, tienda de Libros de Medicina, Libros de Medicina Familiar y Comunitaria/General - Medicina clinica