T cells targeting a neuronal paraneoplastic antigen mediate tumor rejection and trigger CNS autoimmunity with humoral activation Journal Article


Authors: Blachère, N. E.; Orange, D. E.; Santomasso, B. D.; Doerner, J.; Foo, P. K.; Herre, M.; Fak, J.; Monette, S.; Gantman, E. C.; Frank, M. O.; Darnell, R. B.
Article Title: T cells targeting a neuronal paraneoplastic antigen mediate tumor rejection and trigger CNS autoimmunity with humoral activation
Abstract: Paraneoplastic neurologic diseases (PND) involving immune responses directed toward intracellular antigens are poorly understood. Here, we examine immunity to the PND antigen Nova2, which is expressed exclusively in central nervous system (CNS) neurons. We hypothesized that ectopic expression of neuronal antigen in the periphery could incite PND. In our C57BL/6 mouse model, CNS antigen expression limits antigen-specific CD4+ and CD8+ T-cell expansion. Chimera experiments demonstrate that this tolerance is mediated by antigen expression in nonhematopoietic cells. CNS antigen expression does not limit tumor rejection by adoptively transferred transgenic T cells but does limit the generation of a memory population that can be expanded upon secondary challenge in vivo. Despite mediating cancer rejection, adoptively transferred transgenic T cells do not lead to paraneoplastic neuronal targeting. Preliminary experiments suggest an additional requirement for humoral activation to induce CNS autoimmunity. This work provides evidence that the requirements for cancer immunity and neuronal autoimmunity are uncoupled. Since humoral immunity was not required for tumor rejection, B-cell targeting therapy, such as rituximab, may be a rational treatment option for PND that does not hamper tumor immunity.
Keywords: cellular immunity; autoimmunity; humoral immunity; cancer; paraneoplastic neurologic disease
Journal Title: European Journal of Immunology
Volume: 44
Issue: 11
ISSN: 0014-2980
Publisher: Wiley V C H Verlag Gmbh  
Date Published: 2015-11-01
Start Page: 3240
End Page: 3251
Language: English
DOI: 10.1002/eji.201444624
PROVIDER: scopus
PUBMED: 25103845
PMCID: PMC4296561
DOI/URL:
Notes: Export Date: 2 January 2015 -- Source: Scopus
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