Lunes 18 de Febrero de 2008; 16:55 hrs.

CD4 T cells, lymphopenia, and IL-7 in a multistep pathway to autoimmunity

 

• Thomas Calzascia, Marc Pellegrini, Albert Lin, Kristine M. Garza, Alisha R. Elford, Arda Shahinian, Pamela S. Ohashi, and Tak W. Mak. Published online on February 14, 2008. Proc. Natl. Acad. Sci. USA, 10.1073/pnas.0712135105
• There are many inhibitory mechanisms that function at the cellular and molecular levels to maintain tolerance. Despite this, self-reactive clones escape regulatory mechanisms and cause autoimmunity in certain circumstances. We hypothesized that the same mechanisms that permit T cells to expand during homeostatic proliferation may inadvertently promote autoimmunity under certain conditions. One major homeostatic cytokine is IL-7, and studies have linked it or its receptor to the development of multiple sclerosis and other autoimmune diseases. We show in a model of β-islet cell self-reactivity that the transfer of activated autoreactive CD4 T cells can prime and expand endogenous autoreactive CD8 T cells in a CD28- and CD40-dependent manner through the licensing of dendritic cells. Despite this, mice do not develop diabetes. However, the provision of exogenous IL-7 or the physiological production of IL-7 associated with lymphopenia was able to profoundly promote the expansion of self-reactive clones even in the presence of regulatory T cells. Autoimmune diabetes rapidly ensued with CD4 help and the subsequent activation of CD8 T cells, which contributed to disease progression. With the advent of many biologicals targeting TNF, IL-6, and IL-1 and their effective use in the treatment of autoimmune diseases, we propose that IL-7 and its receptor may be promising targets for biological agents in the treatment of autoimmunity.....Más.

 

Martes 12 de Febrero de 2008; 10:09 hrs.

Molecular pathogenesis of emphysema

• Laimute Taraseviciene-Stewart and Norbert F. Voelkel J. Clin. Invest. 118(2): 394-402 (2008). doi:10.1172/JCI31811.

• Emphysema is one manifestation of a group of chronic, obstructive, and frequently progressive destructive lung diseases. Cigarette smoking and air pollution are the main causes of emphysema in humans, and cigarette smoking causes emphysema in rodents. This review examines the concept of a homeostatically active lung structure maintenance program that, when attacked by proteases and oxidants, leads to the loss of alveolar septal cells and airspace enlargement. Inflammatory and noninflammatory mechanisms of disease pathogenesis, as well as the role of the innate and adaptive immune systems, are being explored in genetically altered animals and in exposure models of this disease. These recent scientific advances support a model whereby alveolar destruction resulting from a coalescence of mechanical forces, such as hyperinflation, and more recently recognized cellular and molecular events, including apoptosis, cellular senescence, and failed lung tissue repair,....Más.

 

Lunes 28 de Enero 2008; 12:30 hrs.

Chimerism and Tolerance in a Recipient of a Deceased-Donor Liver Transplant

 

• Stephen I. Alexander, M.B., B.S., Neil Smith, M.B., B.S., et al. N Engl J Med. 2008 Jan 24;358(4):369-74

• Complete hematopoietic chimerism and tolerance of a liver allograft from a deceased male donor developed in a 9-year-old girl, with no evidence of graft-versus-host disease 17 months after transplantation. The tolerance was preceded by a period of severe hemolysis, reflecting partial chimerism that was refractory to standard therapies. The hemolysis resolved after the ...Más.

Lunes 28 de Enero 2008; 12:27 hrs.

Tolerance and Chimerism after Renal and Hematopoietic-Cell Transplantation

 

• Scandling JD, Busque S, Dejbakhsh-Jones S, et al. N Engl J Med. 2008 Jan 24;358(4):362-68.

• We describe a recipient of combined kidney and hematopoietic-cell transplants from an HLA-matched donor. A post-transplantation conditioning regimen of total lymphoid irradiation and antithymocyte globulin allowed engraftment of the donor's hematopoietic cells. The patient had persistent mixed chimerism, and the function of the kidney allograft has been normal for more than 28 months since discontinuation of all immunosuppressive drugs. Adverse events requiring hospitalization were limited to a 2-day episode of fever ...Más.

Lunes 28 de Enero 2008; 12:25 hrs.

HLA-Mismatched Renal Transplantation without Maintenance Immunosuppression

 

• Kawai T, Cosimi AB, Spitzer TR,et al. N Engl J Med. 2008 Jan 24;358(4):353-61.

• Five patients with end-stage renal disease received combined bone marrow and kidney transplants from HLA single-haplotype mismatched living related donors, with the use of a nonmyeloablative preparative regimen. Transient chimerism and reversible capillary leak syndrome developed in all recipients. Irreversible humoral rejection occurred in one patient. In the other four recipients, it was possible to discontinue all immunosuppressive therapy 9 to 14 months after the transplantation, and renal function has remained stable for 2.0 to 5.3 years since transplantation. The T cells from these four recipients, tested in vitro, showed ....Más.

Lunes 28 de Enero 2008; 11:45 hrs.

Role of ABO Secretor Status in Mucosal Innate Immunity and H. pylori Infection

 

• Lindén S, Mahdavi J, Semino-Mora C, Olsen C, Carlstedt I, et al. PLoS Pathogens Vol. 4, No. 1, e2 doi:10.1371/journal.ppat.0040002

• The fucosylated ABH antigens, which constitute the molecular basis for the ABO blood group system, are also expressed in salivary secretions and gastrointestinal epithelia in individuals of positive secretor status; however, the biological function of the ABO blood group system is unknown. Gastric mucosa biopsies of 41 Rhesus monkeys originating from Southern Asia were analyzed by immunohistochemistry. A majority of these animals were found to be of blood group B and weak-secretor phenotype (i.e., expressing both Lewis a and Lewis b antigens), which are also common in South Asian human populations. A selected group of ten monkeys was inoculated with Helicobacter pylori and studied for changes in gastric mucosal glycosylation during a 10-month period. We observed a loss in mucosal fucosylation and concurrent induction and time-dependent dynamics in gastric mucosal sialylation (carbohydrate marker of inflammation), which affect....Más.

Martes 08 Enero 2008; 09:40 hrs.

B-Cell Identity — Commitment Is Not Forever

Stephen L. Nutt, Ph.D.The New England Journal of Medicine 2008; 358:82-83. A general rule of cell biology is that once a cell commits to a particular differentiation pathway, there is no turning back. It is thought that the event triggering differentiation activates a distinct gene-expression program that is restricted by cell type; this program results in epigenetic changes in the DNA and in modification of accompanying proteins that locks in this state. Understanding cell-lineage commitment is important, because it lies at the heart of attempts to reprogram Más.

Martes 08 Enero 2008; 09:28 hrs.

Major Depressive Disorder

R.H. Belmaker, M.D., and Galila Agam, Ph.D. The New England Journal of Medicine 2008; 358:55-68. Depression is related to the normal emotions of sadness and bereavement, but it does not remit when the external cause of these emotions dissipates, and it is disproportionate to their cause. Classic severe states of depression often have no external precipitating cause. It is difficult, however, to draw clear distinctions between depressions.... Más.