OBJECTIVE Immune suppression during critical illness predisposes to serious infections. We sought to determine the mechanisms regulating tolerance and cross-tolerance to common pro-inflammatory danger signals in a model that recapitulates the intact in vivo immune response. MATERIALS AND METHODS Flt3-expanded splenocytes obtained from wild-type or matching IRAK-M knockout (IRAK-M-/-), C57BL/6...

The field of transplantation has come a long way since the first successful kidney transplant performed by Murray and colleagues in 1954. Kidney, heart, lung, and liver transplantation, among other organs, is now routine, and short-term (1 yr) outcomes have steadily improved to rates of 90 to 95% graft survival (http://www.unos.org). Despite these successes, the major shortfall of our current t...

The immune system of vertebrates is designed to protect against invading pathogens. To be able to deal with different antigenic threats, the T cell repertoire is very diverse. This diversity, though useful, can cause autoimmune diseases if any imbalances in the function of the immune system occur. However, the immune system has its own mechanisms for suppressing or regulating the potentially da...

Age-related changes in immune regulation are likely to account for the age-associated increase in serum autoantibody levels and in certain autoimmune disorders, such as myasthenia gravis (MG). To demonstrate directly a loss of immune tolerance in older individuals, responses to the acetylcholine receptor, the autoantigen in MG, were assessed in transgenic mice expressing the Torpedo californica...

Maternal immune tolerance of the fetus is indispensable for a healthy pregnancy outcome. Nowhere is this immune tolerance more important than at the fetal-maternal interface - the decidua, the site of implantation, and placentation. Indeed, many lines of evidence suggest an immunological origin to the common pregnancy-related disorder, pre-eclampsia. Within the innate immune system, decidual NK...

Under immunogenic conditions, both the site of initial Ag exposure and consequent T cell priming in specific draining lymph nodes (LNs) imprint the ensuing immune response with lasting tissue-selective tropism. With respect to immune tolerance, whether the site of tolerance induction leads to compartmentalized or, alternatively, pervasive tolerance has not been formally investigated. Using a mu...

In the CNS, no pathway dedicated to immune surveillance has been characterized for preventing the anti-CNS immune responses that develop in autoimmune neuroinflammatory disease. Here, we identified a pathway for immune cells to traffic from the brain that is associated with the rostral migratory stream (RMS), which is a forebrain source of newly generated neurons. Evaluation of fluorescently la...

Since the concept of immunologic tolerance was discovered in the 1940s, the pursuit of tolerance induction in human transplantation has led to a rapid development of pharmacologic and biologic agents. Short-term graft survival remains an all-time high, but successful withdrawal of immunosuppression to achieve operational tolerance rarely occurs outside of liver transplantation. Collaborative ef...

Moderate physical training enhances the defense mechanisms, while intense physical training induces to immune suppression. The underlying mechanisms are associated with the link between nervous, endocrine, and immune systems. It suggests autonomic patterns and modulation of immune response. Immune cells, when exposed to regular bouts of stress, develop a mechanism of tolerance. In many tissues,...