Specificity and distribution of self-reactive T cells in health and disease
Research area: Cellular Immunology
Group leaders: Federica Sallusto
Status: In progress
Our aim is to develop sensitive methods to study self-reactive T cells in healthy donors and in patients with autoimmune diseases. Since self-reactive T cells may have low avidity and may be present at low frequencies we will combine cell sorting strategies, which highly enrich specific populations, with the T cell library method that allows detection of even low avidity cells. The feasibility of this approach is illustrated by the analysis of T cells from multiple sclerosis (MS) patients that shows that MOG-specific T cells are detectable in most patients and are virtually all present in the CCR6+ memory subset. These findings are consistent with our previous demonstration that CCR6 is required to drive migration of pathogenic T cells in the CNS of mice developing autoimmune encephalomyelitis. We are extending the analysis to other organ-specific autoimmune diseases, in particular pemphigus, for which autoantigens are well characterized, and to other conditions of aberrant responses to self antigens such as Pulmonary alveolar proteinosis, a rare disease characterized by autoantibodies against GM-CSF, and Factor VIII-treated hemofilia in which anti-Factor VIII antibodies develop in response to the therapy.
These studies are done in collaboration with Antonio Uccelli, University of Genova (IT) and Gianna Zambruno, IDI, Rome (IT).
MOG-reactive T cells in MS patients express CCR6. A. T cell libraries were generated from CCR6+ and CCR6- memory T cells from eight MS patients (Pt.1- Pt.8). The libraries were screened with autologous monocytes pulsed with MOG and T-cell proliferation was evaluated using a 3H-thymidine incorporation assay. The dotted line represents the cut off value. B. Frequencies of MOGreactive T cells calculated on the basis of the fraction of negative cultures and the input of cells per culture. Values are expressed per 106 CD4+ T cells.