Functional IFN-gamma memory in CD4+ T cells: Method for improved T cell therapy and disease monitoring in autoimmune diseases

Technology

Functional memory for IFN-gamma production after antigen exposure is established via decreased methylation at the IFNG promotor and CNS-1 region. The technology provides a T cell-specific methylation pattern in ex vivo effector/memory Th1 cells and highlights its dynamic changes during memory Th1 differentiation. In one application, a method by imprinting the specific methylation pattern into naive T cells was developed to generate memory Th1 cells displaying a robust long-term IFN-gamma response after re-activation. Many cell products suffer from decreased activity in the final therapeutic application since cells have lost re-activation capacity after the proliferation process. This method may therefore serve for generation of more effective and homogeneous cell therapy products. Moreover, quantitative DNA methylation analysis of the IFNG promoter and CNS-1 may also serve as a method for qualifying effective memory T cells
In another application, the methylation status of Th1 cells from RA patients in blood and synovial fluid samples is analyzed. Recruitment of Th1 cells to inflamed joints result in a clear change of distribution of these cells between periphery and sites of inflammation. The methylation pattern between samples from RA patients and healthy donors shows significant changes and allows therefore novel methods to monitor patients with autoimmune diseases.