Atherosclerosis is an inflammatory disease. Because high plasma concentrations of cholesterol, in particular those of low-density lipoprotein (LDL) cholesterol, are one of the principal risk factors for atherosclerosis,1 the process of atherogenesis has been considered by many to consist largely of the accumulation of lipids within the artery wall; however, it is much more than that. Despite changes in lifestyle and the use of new pharmacologic approaches to lower plasma cholesterol concentrations,2,3 cardiovascular disease continues to be the principal cause of death in the United States, Europe, and much of Asia.4,5 In fact, the lesions of atherosclerosis represent . . .

https://www.nejm.org/doi/pdf/10.1056/NEJM199901143400207

Atherosclerosis — An Inflammatory Disease

抗原变异可使得多种致病微生物易于逃避宿主免疫应答。表达在感染红细胞表面的恶性疟原虫红细胞表面蛋白1（PfPMP1）与感染红细胞、内皮细胞、树突状细胞以及胎盘的单个或多个受体作用，在黏附及免疫逃避中起关键的作用。每个单倍体基因组var基因家族编码约60种成员，通过启动转录不同的var基因变异体为抗原变异提供了分子基础。

疟原虫var基因转换速率变化导致抗原变异[英]／Paul H, Robert P, Christodoulou Z, et al//Proc Natl Acad Sci U S A

Atherosclerosis is an Inflammatory Disease

One of the mechanisms by which the innate immune system senses the invasion of pathogenic microorganisms is through the Toll-like receptors (TLRs), which recognize specific molecular patterns that are present in microbial components. Stimulation of different TLRs induces distinct patterns of gene expression, which not only leads to the activation of innate immunity but also instructs the development of antigen-specific acquired immunity. Here, we review the rapid progress that has recently improved our understanding of the molecular mechanisms that mediate TLR signalling.

Toll-like receptor signalling

A large number of changes, distant from the site or sites of inflammation and involving many organ systems, may accompany inflammation. In 1930 interest was focused on these changes by the discovery of C-reactive protein (so named because it reacted with the pneumococcal C-polysaccharide) in the plasma of patients during the acute phase of pneumococcal pneumonia.1 Accordingly, these systemic changes have since been referred to as the acute-phase response,2 even though they accompany both acute and chronic inflammatory disorders. New acute-phase phenomena continue to be recognized, and the mechanisms mediating them are becoming better understood. This review summarizes much of . . .

Acute-Phase Proteins and Other Systemic Responses to Inflammation

The role of IL-1 in augmenting the Ag receptor-initiated activation program was evaluated in IL-4-producing (Th2) CD4+ murine T lymphocytes. Northern blot and 125I-labeled IL-1 alpha cross-linking analyses demonstrated that Th2 lymphocytes express both type I and type II IL-1R. The expression of both IL-1R isoforms on the surface of the Th2 cells is coordinately up-regulated in response to anti-CD3 cross-linking in the absence of detectable accessory cells. Analyses of the kinetics of IL-1R acquisition demonstrated that the peak level of type I and type II IL-1R mRNA expression occurs after the peak expression of mRNA encoding IL-2R alpha and IL-4, which are two IL-1-responsive events in the Th2 activation program. Type I IL-1R ligand-binding antagonists, IL-1R antagonist and anti-type I mAb, were used to evaluate the functional significance of Th2 cell expression of two IL-1R isoforms. The addition of either IL-1R antagonist or anti-type I mAb completely inhibited the IL-1 alpha-augmented component of the proliferative response stimulated by anti-CD3 plus exogenous IL-1 alpha. Together, these studies indicate that, although Th2 clones express inducible levels of both type I and type II IL-1R isoforms, the IL-1-induced intracellular signals involved in augmenting an anti-CD3-stimulated proliferative response are mediated solely through the type I IL-1R.

Murine T helper cell-2 lymphocytes express type I and type II IL-1 receptors, but only the type I receptor mediates costimulatory activity.

ST2 ligand polypeptides are provided, along with DNA sequences, expression vectors and transformed host cells useful in producing ST2 ligand polypeptides. The ST2 ligand polypeptide binds to a receptor that is expressed on cell types that include certain Hodgkin's Disease-derived tumor cells.

Cytokine that binds ST2

Monoclonal antibody 1994-01 (also known as ALVA 42) reported to recognize type II IL-1 receptor is specific for HLA-DR alpha and beta chains.

Previous studies have shown that binding of IL-1 to its receptor and intracellular processing of the IL-1/IL-1 receptor complex appear to be different in B- and T-cells. The current report summarizes recent studies from our laboratory that show that the murine and human IL-1 receptors present on T-cells and fibroblasts are identical in primary sequence within each species, and highly similar even when the two species are compared. At present no cDNA clones have been isolated for IL-1 receptors present on B-cells. However, a monoclonal antibody raised to the receptor on murine T-lineage cells did not bind to a pre-B-lymphoma cell line that displays IL-1 binding sites, nor would cDNA probes derived from a T-cell IL-1 receptor clone cross hybridize at high stringency to mRNA prepared from these cells. In addition the two receptors differ substantially in size, as determined by affinity crosslinking with radiolabeled IL-1 alpha. Taken together, these observations show that major structural differences exist between the IL-1 receptors on B and T lymphocytes, while the receptors on T-cells and fibroblasts are identical polypeptides. We propose that the T-cell/fibroblast receptor be called IL-1RI and the B-cell type IL-1RII.

Molecular heterogeneity of interleukin-1 receptors.

Although the proliferation of CD8+ CTL typically requires cytokine support provided by helper T cells, a subset of naturally occurring CD8+ CTL are capable of proliferating independently of T cell help. Such helper-independent CTL have previously been shown to possess IL-1 receptors (IL-1R) and to proliferate in response to IL-1 through endogenous production of IL-2. In this study, we have transduced conventional helper-dependent CTL clones with a retroviral vector encoding the murine type I IL-1R. Transduced CTL selected in G418 expressed vector-derived transcripts encoding IL-1R and displayed approximately 1000 cell surface receptors with an IL-1 affinity typical for the type I IL-1R. In contrast to parental cells, transduced CTL proliferated in response to IL-1 in the presence of Ag, without a requirement for helper T cells, IL-2, or other cytokine support. Stimulation with both IL-1 and Ag was necessary for the proliferative response. No endogenous synthesis of IL-2 could be detected in the IL-1R transduced cells in response to IL-1 stimulation, in the presence or absence of Ag. The IL-1R-induced phenotype was demonstrated in two independent T cell clones, both of which retained Ag-specific cytolytic activity. No such conversion to a helper-independent phenotype was induced by a retroviral vector encoding only the neo gene. The behavior of the IL-1R-transduced CTL in proliferation assays thus resembled that of the naturally occurring helper-independent CTL.

Jennifer L. Slack

Papers

Murine T helper cell-2 lymphocytes express type I and type II IL-1 receptors, but only the type I receptor mediates costimulatory activity.

Cytokine that binds ST2

Monoclonal antibody 1994-01 (also known as ALVA 42) reported to recognize type II IL-1 receptor is specific for HLA-DR alpha and beta chains.

Molecular heterogeneity of interleukin-1 receptors.

Helper T cell-independent proliferation of CD8+ cytotoxic T lymphocytes transduced with an IL-1 receptor retrovirus.