Current Immunology Reviews

ISSN: 1573-3955

Current Immunology Reviews
Volume 3, Number 3, August 2007

Contents


Heterogeneity in the CD4 T Cell Compartment and the Variability of Neonatal Immune Responsiveness Pp. 151-159
Becky Adkins
[Abstract]


Influence of CD80 and CD86 Co-Stimulation in the Modulation of the Activation of Antigen Presenting Cells Pp. 160-169
Manzoor A. Mir and Javed N. Agrewala
[Abstract]


T Cell Polarization and the Formation of Immunological Synapses: From Antigen Recognition to Virus Spread Pp. 170-188
Ana Monica Pais-Correia, Maria Isabel Thoulouze and Andrés Alcover
[Abstract]


Neurotrophins – More than Neurotrophic Pp. 189-215
Shamini Ayyadhury and Klaus Heese
[Abstract]


Islet Inflammation in Type 2 Diabetes (T2D): From Endothelial to β-Cell Dysfunction Pp. 216-232
Jan A. Ehses, Sophie Calderari, Jean-Claude Irminger, Patricia Serradas, Marie-Hélène Giroix, Anja Egli, Bernard Portha, Marc Y. Donath and Françoise Homo-Delarche
[Abstract]




Abstracts

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Heterogeneity in the CD4 T Cell Compartment and the Variability of Neonatal Immune Responsiveness
Becky Adkins

Over the past decade, it has become clear that T cell immune responses in both murine and human neonates are very heterogeneous, running the gamut from poor or deviant responsiveness to mature, adult-like inflammatory function. How this variability arises is not well understood but there is now a great deal of information suggesting that differences in the T cell compartments in neonates vs adults play important roles. A number of cell types or processes are qualitatively or quantitatively different in the neonate. These include (a) alternate epigenetic programs at the Th2 cytokine locus, (b) enhanced homeostatic proliferation, (c) a relative abundance of fetal-origin cells, (d) a greater representation of recent thymic emigrants, (e) high proportions of potentially self-reactive cells, (f) a developmental delay in the production of regulatory T cells, and (g) cells bearing TCR with limited N region diversity. Different conditions of antigen exposure may lead to different environmental signals that promote the selective responsiveness of one or more of these populations. Therefore, the variability of neonatal responses may be a function of the heterogeneous nature of the responding T cell population. In this review, we will describe these various subpopulations in detail and speculate as to the manner in which they could contribute to the heterogeneity of neonatal immune responses.


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Influence of CD80 and CD86 Co-Stimulation in the Modulation of the Activation of Antigen Presenting Cells
Manzoor A. Mir and Javed N. Agrewala

The role of CD80 and CD86 costimulatory molecules is well established in the activation of T cells but not antigen presenting cells. Recently, many reports in literature have demonstrated categorically the influence of CD80 and CD86 in the activation of B cells and dendritic cells. Stimulation via CD80/CD86 in B cells can modulate their proliferation, IgG secretion and expression of pro-apoptotic and anti-apoptotic molecules, nuclear localization of NF-κB p50 subunit, phosphorylation of Rel A (p65) and IκB–alpha and increased oct-2 expression. In case of dendritic cells, it has been shown that signals induced via CD80 and CD86 enhance the production of IL-6 and IFN-γ which in turn, up-regulates the expression of the enzyme indolamine 2, 3-dioxygenase that results in tryptophan catabolism and affects T cell proliferation. Interestingly, it has been shown that co-stimulation through CD80 can restrict the survival of lymphomas and can also induce apoptosis in neural stem cells. Consequently, it may be concluded that CD28/CD152-CD80/86 interaction delivers a bi-directional co-stimulation, thereby not only having impact on the function of T cells, but also antigen presenting cells.


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T Cell Polarization and the Formation of Immunological Synapses: From Antigen Recognition to Virus Spread
Ana Monica Pais-Correia, Maria Isabel Thoulouze and Andrés Alcover

Soon after antigen recognition, T lymphocytes polarize towards antigen presenting cells (APC) and form immunological synapses. The formation of immunological synapses is a complex process that involves T cell signaling, as well as membrane, cytoskeleton and vesicular trafficking events. Immunological synapses are thought to be multitasking molecular arrangements that structure in time and space the complex communication between T lymphocytes and APCs. Lymphotropic viruses, such as the human immunodeficiency virus (HIV), or herpes virus saimiri can impede the formation and function of immunological synapses hence downregulating the capacity of response of infected T lymphocytes. Moreover, retroviruses, like HIV-1, or the human T cell leukemia virus type 1 (HTLV-1), can subvert the mechanism of T cell polarization and immune synapse formation to form organized cell junctions through which these viruses can spread from cell to cell. By analogy to immunological synapses, these viral-induced cell-cell junctions have been called virological synapses. The understanding of the mechanism of generation of immunological synapses versus virological synapses is a fascinating field of study that we will discuss in this review.


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Neurotrophins – More than Neurotrophic
Shamini Ayyadhury and Klaus Heese

The Nerve Growth Factor (NGF) is the prototypic member of the neurotrophin (NT) family, which plays an essential role in the development and functioning of the vertebrate nervous system. Although originally defined by their actions on neuronal survival and differentiation in the peripheral (PNS) and central nervous systems (CNS), accumulating data indicate the presence of extensive interactions between the NTs and the immune system. NTs are released normally during lymphocyte and leukocyte development by the bone marrow and the thymus and later by secondary lymph organs to maintain responsiveness of these circulating naïve and memory immune cells. Functional NT receptors have been detected on the cells of the immune system and increased levels of NGF protein are found during the acute phase of various diseases with a significant inflammatory component. Furthermore, in certain conditions such as allergic asthma, the released NTs exacerbate the severity of the inflammation and prolong the diseased state. However, in the CNS, if one can control homeostasis of the internal environment, then the natural response of the infiltrating immune cells to release these NTs can be used to intervene at key points in the disease progression. These wider functions are likely to be of concern in any attempted therapeutic use of NGF or related NTs.


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Islet Inflammation in Type 2 Diabetes (T2D): From Endothelial to β-Cell Dysfunction
Jan A. Ehses, Sophie Calderari, Jean-Claude Irminger, Patricia Serradas, Marie-Hélène Giroix, Anja Egli, Bernard Portha, Marc Y. Donath and Françoise Homo-Delarche

Activation of the innate immune system has been recognized as being associated with T2D patients and those being at increased disease risk. Here we show that inflammation takes place in pancreatic islets both in various T2D animal models and in patients, as reflected by the presence of immune cells and various cytokines and chemokines. Under situations of metabolic stress particularly, islet endocrine cells are a source of cytokine and chemokine production, but other pancreatic islet cells such as immune, endothelial and neuronal cells may also be involved. Notably, in various T2D animal models (and probably in humans too), a process of microangiopathy with subsequent fibrosis takes place that results in islet blood flow alterations and eventually leads to a loss of islet architecture. Taking into account that the microvasculature plays an integral role in islet function and that cytokines are deleterious for β -cells, we suggest that endothelial-islet inflammation might contribute to β -cell impairment in T2D. This hypothesis is supported by the fact that treatments that preserve islet architecture and ameliorate endothelial dysfunction, improve β -cell function. Better understanding of the mechanisms involved in early β -cell failure should lead to the identification of new therapeutic targets for the prevention and treatment of T2D.