Upon antigen encounter, naïve T cells differentiate into (i) effectors that combat infected or malignant cells, and at later time points, into (ii) memory cells that provide long-lasting immunity. This differentiation process allows some T cells to leave the confines of secondary lymphoid organs and to enter peripheral tissues in search of pathogens or tumor cells. These different environments pose specific challenges for effector and memory T cells to maintain homeostasis. T cells directed into the lungs are likely to encounter higher levels of oxygen, but lower amounts of nutrients than those directed into the intestinal epithelium. In addition to oxygen tension and nutrient concentrations, other key factors, such as the commensal flora and stromal components, create unique conditions that require tissue-specific adaptations of T cells. These steady state conditions can dramatically change during infection when inflammatory mediators and T cell growth factors are released, requiring the immediate response of T cells. The gradual changes imposed by growing tumors can also be challenging for T cells due to competition with rapidly cycling tumor cells that deplete essential resources of oxygen and glucose. The strategies that T cells employ to respond to the diverse cues from their surroundings are the focus of current research. It appears that next to circulating memory T cells that are confined to the circulation and those that survey all of the peripheral tissues, dedicated populations of resident memory T cells exist that can optimally adapt to the local circumstances within each tissue. Restrictions on the metabolic requirements of T cells residing in tumor tissue have been found to directly impact on effector functions such as cytokine production. The fundamental principles of how the machinery of T cells can translate local cues into tissue-specific differentiation processes are fascinating and warrant further investigation.

Persistent Viral Infections Edited by Rafi Ahmed Emory Vaccine Center, Atlanta, USA and Irvin S. Y. Chen UCLA School of Medicine, Los Angeles, USA During the past decade much of our attention has focused on diseases associated with viral persistence. Major breakthroughs in immunology, and the advent of molecular approaches to study pathogenesis have increased our understanding of the complex virus-host interactions that occur during viral persistence. Persistent Viral Infections focuses on: * The pathogenesis and immunology of chronic infections * Animal models that provide, or have the potential to provide, major insights This volume will be essential reading for virologists, immunologists, oncologists and neurologists.

T cells play a vital role mediating adaptive immunity, a specific acquired resistance to an infectious agent produced by the introduction of an antigen. There are a variety of T cell types with different functions. They are called T cells, because they are derived from the thymus gland. This volume discusses how T cells are regulated through the operation of signaling mechanisms. Topics covered include positive and negative selection, early events in T cell receptor engagement, and various T cell subsets.

The Janeway's Immunobiology CD-ROM, Immunobiology Interactive, is included with each book, and can be purchased separately. It contains animations and videos with voiceover narration, as well as the figures from the text for presentation purposes.

The vertebrate immune system defends the organism against invading pathogens while at the same time being self-tolerant to the body’s own constituents thus preserving its integrity. Multiple mechanisms work in concert to ensure self-tolerance. Apart from purging the T cell repertoire from auto-reactive T cells via negative selection in the thymus dominant tolerance exerted by regulatory T cells plays a major role in tolerance imposition and maintenance. Among the various regulatory/suppressive cells hitherto described, CD4+CD25+ regulatory T cells (Treg) and interleukin-10 producing T regulatory 1 (Tr1) cells have been studied in most detail and are the subject of most articles in this issue. Treg, also called "natural" regulatory T cells, will be traced from their intra-thymic origin to the site of their action in peripheral lymphoid organs and tissues. The repertoire of Treg is clearly biased towards recognition of self-antigens, thereby potentially preventing autoimmune diseases such as gastritis and oophoritis. Regulatory T cells, however also control infections, allergies and tolerance to transplanted tissues and this requires their induction in the periphery under conditions which are not yet fully understood. The concept of dominant tolerance, by far not novel, will offer new insights and hopefully tools for the successful treatment of autoimmune diseases, improved cancer immunotherapy and transplant survival. The fulfillment of these high expectations will, however, require their unambiguous identification and a better understanding of their mode of action.