Interleukin-2 deficiency-induced T cell autoimmunity in the mouse brain.
Interleukin-2 (IL-2) has been implicated in the pathogenesis of neurodevelopmental and neurodegenerative disorders. Studies from our lab have shown that adult IL-2 knockout (KO) mice exhibit septohippocampal pathology and related behavioral deficits. Compared to IL-2 wild-type (WT) mice, IL-2 KO mice have a marked and selective loss of septal cholinergic neurons that occurs between the third postnatal week and adulthood. Given that the development of septal neurons is completed by embryonic day 17 and that IL-2 KO mice exhibit peripheral autoimmunity that develops progressively post-weaning, our data and others led us to postulate that the loss of septal neurons in adult IL-2 KO mice is due to selective autoimmune neurodegeneration that coincides with increasing levels of peripheral autoimmunity. Thus, the present study tested the hypotheses: (1) that T cells selectively target the septum, and; (2) that T lymphocyte infiltration to the septum would correlate with peripheral autoimmune disease. We quantified CD3(+) T cells in the septum, hippocampus, and cerebellum of IL-2 KO and IL-2 WT mice at ages ranging from 2 to 14 weeks. T cells infiltrated the brains of IL-2 deficient mice, but were not selective for the septum. Brain T lymphocyte levels in IL-2 KO mice correlated positively with the degree of peripheral autoimmunity. We did not detect CD19(+) B lymphocytes, IgG-positive lymphocytes or IgG deposition indicative of autoantibodies in the brains of IL-2 KO mice. Further study is needed to understand how IL-2 deficiency-induced autoimmune T lymphocytes interact with endogenous brain cells to alter function and promote disease.
Huang
Zhi
Z
Department of Psychiatry, McKnight Brain Institute, University of Florida Gainesville, FL, USA.
Dauer
Daniel J
DJ
Ha
Grace K
GK
Lewis
Mark H
MH
Petitto
John M
JM
D000818:Animals; D015551:Autoimmunity; D001921:Brain / Q000276:immunology* / Q000473:pathology; D002465:Cell Movement; D002531:Cerebellum / Q000276:immunology / Q000473:pathology; D006624:Hippocampus / Q000276:immunology / Q000473:pathology; D007376:Interleukin-2 / Q000235:genetics / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D020721:Nervous System Autoimmune Disease, Experimental / Q000276:immunology* / Q000473:pathology; D009474:Neurons / Q000473:pathology; D009929:Organ Size; D020665:Septum of Brain / Q000276:immunology / Q000473:pathology; D013154:Spleen / Q000276:immunology / Q000473:pathology; D013601:T-Lymphocytes / Q000276:immunology* / Q000502:physiology
D007376:Interleukin-2