Functional role of skin resident effector memory T cells in host protection against infections and behaviour in healthy skin and cutaneous lymphomas.

• Applicant: Dr. Emmanuella Guenova-Hötzenecker
• Subject Area: Dermatology
• Term: from 2012 to 2014
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 209176247

It is now believed that two different types of memory T cells (effector memory (TEM) and central memory T cells (TCM) exist. It has been suggested that TCM are the only long-lived reservoirs of immunologic memory, while effector T cells of all types are short-lived cells that disappear from the blood and tissues following resolution of immune responses. This opinion predates the findings that epithelial tissues, including the skin, actually contain large numbers of T cells even in the absence of active inflammation. Cutaneous T-cell lymphomas (CTCL) are a group of non-Hodgkin lymphomas derived from skin homing and skin resident T cells. The prognosis for patients with advanced CTCL is poor: patients often die of infection and most systemic therapies are not effective. Depletion of CD52+ cells (all circulating lymphocytes) induces complete remission in >75% of advanced stage CTCL patients. Surprisingly, and despite the fact that these patients have no circulating T or B cells, the incidence of infections is not increased. We hypothesize that anti-CD52 actually selectively depletes TCM from human skin, while leaving skin resident TEM unaffected. These remaining skin resident TEM provide local immune protection and prevent cutaneous infections even in the absence of circulating T and B cells. Data from mouse models corroborate this hypothesis. Yet, because of the lack of appropriate human study model, critical questions on memory T cells have never been addresses in humans: i) are human TCM a migratory cell type that continually recirculate between the skin, blood and lymph nodes, whereas human TEM are a sessile non-migratory T cells? ii) can human TEM mediate host protection against infection in the absence of contribution from the circulating TCM population? In the presented project we will address these points using anti-CD52 mediated T cell depletion in CTCL patients as a best suited model to study the basic biology and immunology of human memory T cells.

• DFG Programme: Research Fellowships
• International Connection: USA
• Host: Professor Dr. Thomas Kupper