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Schnurri (Shn) is a large zinc-finger containing protein, which plays a critical role in cell growth, signal transduction and lymphocyte development. There are three orthologues (Shn-1, Shn-2 and Shn-3) in vertebrates. In Shn-2-deficient mice, the activation of NF-κB in CD4 T cells is upregulated and their ability to differentiate into Th2 cells is enhanced in part through the increased...
Naïve CD8 T cells differentiate in response to antigen stimulation. They acquire the capacity to express multiple effector molecules and mediate effector functions that contribute to infection control. Once antigen loads are reduced they revert progressively to a less activated status and eventually reach a steady-state referred to as “memory” that is very different from that of naïve cells. Indeed,...
The current literature on the role of interleukin (IL)-2 in memory CD8+ T-cell differentiation indicates a significant contribution of IL-2 during primary and also secondary expansion of CD8+ T cells. IL-2 seems to be responsible for optimal expansion and generation of effector functions following primary antigenic challenge. As the magnitude of T-cell expansion determines the numbers of...
Following infection or vaccination, antigen-specific T cells undergo enormous expansion in numbers and differentiate into effector cells that control infection and modulate other aspects of innate and adaptive immunity. The effector T-cell expansion phase is followed by an abrupt period of contraction, during which 90–95% of antigen-specific T cells are eliminated. The surviving pool of...
Memory T-cell generation is limited by activation-induced cell death during the effector T-cell stage. Cell surface proteins are known to transmit signals that either accentuate or limit T-cell death after activation. This chapter will focus on the TNF-receptor family member OX40, which is expressed on effector T cells and when engaged greatly enhances survival of T cells leading to increased...
Immunological memory is considered the hallmark of adaptive, or acquired, immunity. That ability of our immune system to recognize and respond to those pathogens we have encountered before not only typifies acquired immunity but has provided the basis for the most notable of medical interventions: vaccination. Yet, as much as we now know about this process, we are still on the cusp of fully...
CD8 T-cell responses play an important role in protection against intracellular pathogens. Memory CD8 T cells mediate rapid clearance of pathogens upon secondary infection owing to their elevated frequency, ready localization to peripheral sites of infection and their ability to rapidly expand and mount effector functions. Such potent long-lasting protective memory CD8 T cells develop in...
Investigation of T-cell-mediated immunity following acute viral infection represents an area of research with broad implications for both fundamental immunology research as well as vaccine development. Here, we review techniques that are used to assess T-cell memory including limiting dilution analysis, enzyme-linked immunospot (ELISPOT) assays, intracellular cytokine staining (ICCS) and...
Memory T-cell responses are of vital importance in understanding the host’s immune response against pathogens and cancer cells and to begin establishing the correlation of protection against disease. In this review, we discuss our own data in the general context of current knowledge to sketch tentative working principles for the induction of protective T-cell responses by vaccination. We...
The Rhesus macaque (Macaca mulatta) is one of the best studied species of Old World monkeys. DNA sequencing of the entire Rhesus macaque genome, completed in 2007, has demonstrated that humans and macaques share about 93% of their nucleotide sequence. Rhesus macaques have been widely used for medical research including drug testing, neurology, behavioral and cognitive science, reproduction,...
Parasitic infections remain a major health problem throughout the world and unlike many viral or bacterial diseases, there are no vaccines to help control parasitic diseases. While several important advances have been made that will contribute to the development of parasite vaccines, such as cloning of dominant parasite antigens and a better understanding of the effector T-cell subsets needed...
Memory T-cell responses to cancer antigens may be an effective way to sustain long-term tumor-free survival. However, finding an effective vaccination strategy to induce memory T-cell responses toward tumor associated antigens in patients with existing disease has proven to be extremely difficult. Immune stimulation regimens have been combined with tumor vaccination in an attempt to boost the immune...
Cancer is a major public health problem worldwide. Accumulating evidence suggests that tumor-host interactions may in part impact on tumor progression. However, the role of inflammation and adaptive immune reaction in cancer emergence, local and metastatic invasion and recurrence are still not clearly defined. Pro-inflammatory mediators are suspected to favor tumor growth and angiogenesis...
Over the past several years, progress in the field of tumor immunology has lead to advances in active immunotherapy and vaccination as a means of eliciting tumor-specific immune responses to mediate tumor regression and clearance. Developing vaccines targeted against cancer became an important focus as a therapy following the success of viral vaccines in preventing infection and disease...
Evidence is accumulating that old individuals are more susceptible to infection with organisms to which they were previously immune, indicating that there might be a limit to the persistence of immune memory. The prevailing concept is that defects in memory T-cell populations result from inexorable end-stage differentiation as a result of repeated lifelong antigenic challenge. We discuss...
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