Requirements of T celldriven Autoimmunity in Alymphoplastic Mice: Dissertation, University Zurich, Experimental Immunology, 201,Used

Requirements of T celldriven Autoimmunity in Alymphoplastic Mice: Dissertation, University Zurich, Experimental Immunology, 201,Used

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Secondary lymphoid tissues (SLTs) are an absolute requirement for lymphocyte activation. Alymphoplastic (NIKaly/aly) mice lack lymph nodes and display impaired immunity. The malformations of NIKaly/aly mice are due to a mutation in the NFkBinducing kinase (NIK). NIK is involved in the formation of SLTs during development. To our surprise, we found that the immunodeficiency of NIKaly/aly mice results from the impact of NIK on T cell priming but not from the lack of SLTs. We describe an alternative pathway for the induction of cellmediated immunity, in which antigenpresenting cells sample antigen and migrate into the liver where they induce neolymphoid aggregates. We further demonstrate that the NIKlesion in NIKaly/aly mice does not cause an intrinsic T cell defect but leads to the failure of dendritic cells to licence CD4+ effector lineages. In detail we discovered that a population of thymic DCs requires NIK and is capable to shape the formation of T effector lineages during thymic T cell development.

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