The long term objective of the research proposal is to study the role of chemokines and their receptors in the pathogenesis of lymphocytic interstitial pneumonitis which develop in transgenic mice expressing some of the HIV-1 genes in specific immune cells (immature CD4+CD8+ T cells, mature CD4+ T cells and cells of the macrophage/dendritic lineage. Our central hypothesis is that this lung disease is immune-mediated and is driven by the recruitment of immune cells in the lung through the action of specific chemokines. In humans infected with HIV-1 and having lymphocytic interstitial pneumonitis, the main population of immune cells found in the lung are the CD8+ T cells. Because the lung lesions of these Tg mice are associated with many other phenotypes very similar to those found in humans infected with HIV-1, we postulate that this model of lung disease is relevant to the lymphocytic interstitial pneumonitis associated with HIV-1 in humans, especially in children. To understand the pathogenesis of this lung disease, we intend: 1- To identify and quantitate the immune cells in the lung. 2- To determine whether these mice exhibit a specific lung microenvironment favoring homing of specific immune cells. 3- To identify the chemokines produced in the lung of these Tg mice. 4- To determine whether blocking or deleting specific chemokines or their receptors and overexpressing some chemokine receptors alter the development of lymphocytic interstitial pneumonitis.
| Priceputu, Elena; Rodrigue, Isabelle; Chrobak, Pavel et al. (2005) The Nef-mediated AIDS-like disease of CD4C/human immunodeficiency virus transgenic mice is associated with increased Fas/FasL expression on T cells and T-cell death but is not prevented in Fas-, FasL-, tumor necrosis factor receptor 1-, or interleukin-1be J Virol 79:6377-91 |
