T Cells, B Cells, Polarized Immune Response in Fibrosis, Systemic Sclerosis: T cells and Polarized Responses
Posted Oct 30 2010 12:00am
T cells and Polarized Responses
Almost three decades ago, microscopic and ultrastructural studies in early scleroderma skin revealed the presence of inflammatory cells, including T cells, preceding the deposition of extracellular matrix and the ultrastructural modifications typical of SSc endothelial cells. The presence of T cells in tissues undergoing fibrotic changes raises two sets of questions. The first is whether T cells accumulate in response to specific antigenic challenges, which in the case of SSc could be autoantigens. The second is whether the functional characteristics of infiltrating T cells may provide useful information to understand fibrosis development and actually whether they may lead to fibrosis - an issue unresolved, yet.
T Cell Antigen Specificity in Systemic Sclerosis and Allied Conditions
Restricted usage of T cell receptor (TCR), indicating antigen-driven T cell expansion, has been documented both in SSc skin and lung. However, no progress has been made in identifying the responsible antigen(s). An interesting approach has been taken in idiopathic pulmonary fibrosis (IPF), in which CD4+ T cells from pulmonary hilar lymph nodes were shown to proliferate when stimulated with IPF but not with normal or other disease lung extracts. These results point to an autoreactive immune process. Others have immunized mice, including strains prone to develop autoimmunity, with human DNA-topoisomerase I (topo-I), an autoantigen targeted by autoantibodies in a subset of SSc patients. Mice developed T cell responses and antibodies against murine topo-I; however, they did not develop pathologic features resembling SSc. This sobering evidence indicates that although tolerance can be broken, it does not directly result in disease development.
Read More...T Cell Functional Characteristics in Systemic Sclerosis and Animal Models