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EN
The immune response triggered following pathogen recognition, though required to clear the infection, can be detrimental if it is produced in excess or fails to resolve promptly. Excessive inflammation contributes to infectious and noninfectious pathologies in the gut (such as inflammatory bowel disease), lung (such as bronchiolitis), and in a variety of autoimmune conditions. T cells contribute significantly to pathology during inflammation. Global anti-inflammatory strategies can alleviate the consequences of exuberant inflammation by suppressing T cell activity, but may leave the patient vulnerable to opportunistic infection. More specific therapies aim to suppress only those T cells involved in the disease process, and one such approach is to target late costimulatory molecules. These are not expressed on na?ve or resting memory cells. Rather, they have a specific window of expression and their ligation results in the production of abundant inflammatory cytokines. By targeting these molecules, it is hoped that inflammation will reduce, but that therapies will be specific enough to avoid, global immune suppression. This review focuses on the late costimulatory molecule OX40, compare it with other T cell costimulators, and highlight why it is a more suitable target for immune intervention than other immune suppressive strategies.
EN
Cytokines are small proteins or glycoproteins that transmit information from one cell to another. Most cells in the body secrete and respond to cytokines and their effects have been described on a myriad of cellular functions. Cytokine interactions may not be linear, thus making the system extremely intricate and with unpredictable features. Therefore, each model of disease may be unique with its own mechanism of autoregulation dictated by positive and negative feedback involving cytokines and costimulatory molecules. The emergence of some cytokines over others in the course of C. neoformans infection may characterize a positive or negative outcome of cryptococcosis. Much less is known about the influence of costimulatory molecules in regulating C. neoformans immune response. The available information indicates a critical role for proinflammatory cytokines such as tumor necrosis factor- and interleukin (IL)-12. The positive role of interferon- in infected tissue as an inducer of antimicrobial function of innate immune cells and as positive feedback for IL-12 induction appears to be indisputable. In vitro studies indicate that costimulatory molecule expression appears to be regulated on antigen presenting cells by C. neoformans and increased expression of B7-1 and CD40 on these cells may promote a protective response. These studies await confirmation in an in vivo system. The interplay between cytokines and costimulatory molecules has been scarcely explored, and additional details are needed to better understand how they convey positive and negative information to immune cells in response to C. neoformans.
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vol. 48
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issue 1
11-19
EN
Systemic lupus erythematosus is a common and often devastating systemic autoimmune disease of unknown etiology. In this communication we review the latest developments of the molecular pathogenesis of human lupus. Novel genetic studies of multiplex lupus families have revealed potential disease-associated genome intervals, put special emphasis on genetic loci mapping in the long arm of chromosome 1 and have underscored the complexity of the underlying genetic background. New data have emerged on the role of estrogens in the function of lymphocytes and a number of studies have recently emphasized the relative Th-1/Th-2 cytokine imbalance in favor of a Th-2 type cytokine immune response. Finally, novel experiments have revealed an abnormal antigen receptor- -mediated signaling process in lupus T and B cells, which may influence the aberrant expression and function of costimulatory molecules as well as of other aspects of immune cell function. It is important to decipher the underlying molecular mechanisms that govern the expression of human lupus, because we may design novel, rational approaches in the treatment of a human lupus, a disease that has high morbidity and mortality.
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