title: CD4+ and CD8+ T cells are both needed to induce paraneoplastic neurological disease in a mouse model.
abstract: Paraneoplastic neurological disorders (PNDs) are rare human autoimmune diseases that mostly affect the central nervous system (CNS). They are triggered by an efficient immune response against a neural self-antigen that is ectopically expressed in neoplastic tumors. Due to this shared antigenic expression, the immune system reacts not only to tumor cells but also to neural cells resulting in neurological damage. Growing data point to a major role of cell-mediated immunity in PNDs associated to autoantibodies against intracellular proteins. However, its precise contribution in the pathogenesis remains unclear. In this context, our study aimed at investigating the impact of anti-tumor cellular immune responses in the development of PND. To this end, we developed an animal model mimicking PND. We used a tumor cell line expressing the hemagglutinin (HA) ofinfluenzavirus to induce an anti-tumor response in CamK-HA mice, which express HA in CNS neurons. To promote and track the T cell response against the HA antigen, naïve HA-specific CD8+ and/or CD4+ T cells, originating from TCR-transgenic animals, were transferred into these mice. We demonstrate that HA-expressing tumors, but not control tumors, inducein vivoactivation, proliferation and differentiation of naïve HA-specific CD4+ and CD8+ T cells into effector cells. Moreover, both T cell subsets were needed to control tumor growth and induce CNS inflammation in CamK-HA mice. Thus, this new mouse model provides further insight into the cellular mechanisms whereby a potent anti-tumor immunity triggers a cancer-associated autoimmune disease, and may therefore help to develop new therapeutic strategies against PND.
authors.affiliation: INSERM UMR1043 - CNRS U5282, Centre de Physiopathologie Toulouse-Purpan, Toulouse, France; Université Toulouse III, Tolouse, France.
authors.forename: Christina
authors.initials: C
authors.lastname: Gebauer
authors.affiliation: INSERM UMR1043 - CNRS U5282, Centre de Physiopathologie Toulouse-Purpan, Toulouse, France; Université Toulouse III, Tolouse, France; Department of Clinical Neurosciences, Toulouse University Hospital, Toulouse, France.
authors.forename: Béatrice
authors.initials: B
authors.lastname: Pignolet
authors.affiliation: INSERM UMR1043 - CNRS U5282, Centre de Physiopathologie Toulouse-Purpan, Toulouse, France; Université Toulouse III, Tolouse, France; Institute of Biomedical Sciences I, University of São Paulo, São Paulo, Brazil.
authors.forename: Lidia
authors.initials: L
authors.lastname: Yshii
authors.affiliation: INSERM UMR1043 - CNRS U5282, Centre de Physiopathologie Toulouse-Purpan, Toulouse, France; Université Toulouse III, Tolouse, France.
authors.forename: Emilie
authors.initials: E
authors.lastname: Mauré
authors.affiliation: Department of Neuroimmunology, Center for Brain Research, Medical University of Vienna , Vienna, Austria.
authors.forename: Jan
authors.initials: J
authors.lastname: Bauer
authors.affiliation: INSERM UMR1043 - CNRS U5282, Centre de Physiopathologie Toulouse-Purpan, Toulouse, France; Université Toulouse III, Tolouse, France.
authors.forename: Roland
authors.initials: R
authors.lastname: Liblau
keywords: Autoimmunity; T cells; central nervous system; paraneoplastic neurological disease; tumor immunity