Kurzfassung

(SFB/TR128, Teilprojekt A09)
Multiple Sclerosis (MS) is considered to be an inflammatory autoimmune disease resulting from different subsets of autoreactive T effector cells (Teff) usually kept in balance by natural and inducible regulatory cells. Our groups have contributed to the identification and characterization of basic mechanisms of peripheral immune regulation in humans, its pathological alterations in MS, and pathways of therapeutic modification to re-induce tolerance. Previous data...(SFB/TR128, Teilprojekt A09)
Multiple Sclerosis (MS) is considered to be an inflammatory autoimmune disease resulting from different subsets of autoreactive T effector cells (Teff) usually kept in balance by natural and inducible regulatory cells. Our groups have contributed to the identification and characterization of basic mechanisms of peripheral immune regulation in humans, its pathological alterations in MS, and pathways of therapeutic modification to re-induce tolerance. Previous data related to this project demonstrate that peripheral T cell responses are altered in MS. Our preliminary data suggest that both CD4+ and CD8+ Teff are insufficiently regulated and partially resistant to suppressive activity by Foxp3+ Treg. Plasmacytoid dendritic cells (pDC) consist of at least two definable subsets, tolerogenic pDC1 and proinflammatory pDC2. In MS patients, the pDC2 subset dominates, thus influencing the balance of pro-and anti-inflammatory T cell responses. In this project, we intend to (i) analyze Teff properties and their regulation in peripheral blood of MS patients, (ii) investigate the role of pDC subsets in modulating Teff activities of MS patients, and (iii) develop and improve a humanized mouse model to assess human T cell functions and its modulation in vivo.
Laufzeit: 2012-2016
Projektleiter: HD Dr. Helmut Jonuleit
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