Ajami B, Samusik N, Wieghofer P, Ho PP, Crotti A, Bjornson Z et al (2018) Single-cell mass cytometry reveals distinct populations of brain myeloid cells in mouse neuroinflammation and neurodegeneration models. Nat Neurosci 21(4):541–551. https://doi.org/10.1038/s41593-018-0100-x

Article  CAS  PubMed  PubMed Central  Google Scholar 

Akiyama H, Barger S, Barnum S, Bradt B, Bauer J, Cole GM et al (2000) Inflammation and Alzheimer’s disease. Neurobiol Aging 21(3):383–421. https://doi.org/10.1016/s0197-4580(00)00124-x

Article  CAS  PubMed  PubMed Central  Google Scholar 

Alves S, Churlaud G, Audrain M, Michaelsen-Preusse K, Fol R, Souchet B et al (2017) Interleukin-2 improves amyloid pathology, synaptic failure and memory in Alzheimer’s disease mice. Brain 140(3):826–842. https://doi.org/10.1093/brain/aww330

Article  PubMed  Google Scholar 

Baek H, Ye M, Kang GH, Lee C, Lee G, Choi DB et al (2016) Neuroprotective effects of CD4+CD25+Foxp3+ regulatory T cells in a 3xTg-AD Alzheimer’s disease model. Oncotarget 7(43):69347–69357. https://doi.org/10.18632/oncotarget.12469

Article  PubMed  PubMed Central  Google Scholar 

Baruch K, Rosenzweig N, Kertser A, Deczkowska A, Sharif AM, Spinrad A et al (2015) Breaking immune tolerance by targeting Foxp3 (+) regulatory T cells mitigates Alzheimer’s disease pathology. Nat Commun 6:7967. https://doi.org/10.1038/ncomms8967

Article  CAS  PubMed  Google Scholar 

Beers DR, Henkel JS, Zhao W, Wang J, Huang A, Wen S et al (2011) Endogenous regulatory T lymphocytes ameliorate amyotrophic lateral sclerosis in mice and correlate with disease progression in patients with amyotrophic lateral sclerosis. Brain 134(Pt 5):1293–1314. https://doi.org/10.1093/brain/awr074

Article  PubMed  PubMed Central  Google Scholar 

Bonotis K, Krikki E, Holeva V, Aggouridaki C, Costa V, Baloyannis S (2008) Systemic immune aberrations in Alzheimer’s disease patients. J Neuroimmunol 193(1–2):183–187. https://doi.org/10.1016/j.jneuroim.2007.10.020

Article  CAS  PubMed  Google Scholar 

Boyman O, Sprent J (2012) The role of interleukin-2 during homeostasis and activation of the immune system. Nat Rev Immunol 12(3):180–190. https://doi.org/10.1038/nri3156

Article  CAS  PubMed  Google Scholar 

Dansokho C, Ait Ahmed D, Aid S, Toly-Ndour C, Chaigneau T, Calle V et al (2016) Regulatory T cells delay disease progression in Alzheimer-like pathology. Brain 139(Pt 4):1237–1251. https://doi.org/10.1093/brain/awv408

Article  PubMed  Google Scholar 

Dardalhon V, Korn T, Kuchroo VK, Anderson AC (2008) Role of Th1 and Th17 cells in organ-specific autoimmunity. J Autoimmun 31(3):252–256. https://doi.org/10.1016/j.jaut.2008.04.017

Article  CAS  PubMed  PubMed Central  Google Scholar 

Ethell DW, Shippy D, Cao C, Cracchiolo JR, Runfeldt M, Blake B et al (2006) Abeta-specific T-cells reverse cognitive decline and synaptic loss in Alzheimer’s mice. Neurobiol Dis 23(2):351–361. https://doi.org/10.1016/j.nbd.2006.03.008

Article  CAS  PubMed  Google Scholar 

Ferretti MT, Merlini M, Spani C, Gericke C, Schweizer N, Enzmann G et al (2016) T-cell brain infiltration and immature antigen-presenting cells in transgenic models of Alzheimer’s disease-like cerebral amyloidosis. Brain Behav Immun 54:211–225. https://doi.org/10.1016/j.bbi.2016.02.009

Article  CAS  PubMed  Google Scholar 

Gallagher JJ, Finnegan ME, Grehan B, Dobson J, Collingwood JF, Lynch MA (2012) Modest amyloid deposition is associated with iron dysregulation, microglial activation, and oxidative stress. J Alzheimers Dis 28(1):147–161. https://doi.org/10.3233/JAD-2011-110614

Article  CAS  PubMed  Google Scholar 

Garcia JA, Cardona SM, Cardona AE (2014) Isolation and analysis of mouse microglial cells. Curr Protoc Immunol 104:14–35. https://doi.org/10.1002/0471142735.im1435s104

Article  Google Scholar 

Hardy J, Selkoe DJ (2002) The amyloid hypothesis of Alzheimer’s disease: progress and problems on the road to therapeutics. Science 297(5580):353–356. https://doi.org/10.1126/science.1072994

Article  CAS  PubMed  Google Scholar 

He J, Zhang X, Wei Y, Sun X, Chen Y, Deng J et al (2016) Low-dose interleukin-2 treatment selectively modulates CD4 (+) T cell subsets in patients with systemic lupus erythematosus. Nat Med 22(9):991–993. https://doi.org/10.1038/nm.4148

Article  CAS  PubMed  Google Scholar 

Hemonnot AL, Hua J, Ulmann L, Hirbec H (2019) Microglia in Alzheimer Disease: well-known targets and new opportunities. Front Aging Neurosci 11:233. https://doi.org/10.3389/fnagi.2019.00233

Article  CAS  PubMed  PubMed Central  Google Scholar 

Jankowsky JL, Fadale DJ, Anderson J, Xu GM, Gonzales V, Jenkins NA et al (2004) Mutant presenilins specifically elevate the levels of the 42 residue beta-amyloid peptide in vivo: evidence for augmentation of a 42-specific gamma secretase. Hum Mol Genet 13(2):159–170. https://doi.org/10.1093/hmg/ddh019

Article  CAS  PubMed  Google Scholar 

Klatzmann D, Abbas AK (2015) The promise of low-dose interleukin-2 therapy for autoimmune and inflammatory diseases. Nat Rev Immunol 15(5):283–294. https://doi.org/10.1038/nri3823

Article  CAS  PubMed  Google Scholar 

Kopec KK, Carroll RT (1998) Alzheimer’s beta-amyloid peptide 1–42 induces a phagocytic response in murine microglia. J Neurochem 71(5):2123–2131. https://doi.org/10.1046/j.1471-4159.1998.71052123.x

Article  CAS  PubMed  Google Scholar 

Korin B, Ben-Shaanan TL, Schiller M, Dubovik T, Azulay-Debby H, Boshnak NT et al (2017) High-dimensional, single-cell characterization of the brain’s immune compartment. Nat Neurosci 20(9):1300–1309. https://doi.org/10.1038/nn.4610

Article  CAS  PubMed  Google Scholar 

Kosmaczewska A (2014) Low-dose interleukin-2 therapy: a driver of an imbalance between immune tolerance and autoimmunity. Int J Mol Sci 15(10):18574–18592. https://doi.org/10.3390/ijms151018574

Article  CAS  PubMed  PubMed Central  Google Scholar 

Laurence A, Tato CM, Davidson TS, Kanno Y, Chen Z, Yao Z et al (2007) Interleukin-2 signaling via STAT5 constrains T helper 17 cell generation. Immunity 26(3):371–381. https://doi.org/10.1016/j.immuni.2007.02.009

Article  CAS  PubMed  Google Scholar 

Liesz A, Suri-Payer E, Veltkamp C, Doerr H, Sommer C, Rivest S et al (2009) Regulatory T cells are key cerebroprotective immunomodulators in acute experimental stroke. Nat Med 15(2):192–199. https://doi.org/10.1038/nm.1927

Article  CAS  PubMed  Google Scholar 

Lv C, Zhang H, Li Z, Zhang H, Zhang Y, Li R et al (2021) Low-dose IL-2 therapy compensates for metabolic shifts and reverses anxiety-like behavior in PD-1 deficiency-induced autoimmunity. Cell Mol Immunol 18(5):1336–1338. https://doi.org/10.1038/s41423-020-00562-y

Article  CAS  PubMed  Google Scholar 

Michalek RD, Gerriets VA, Jacobs SR, Macintyre AN, MacIver NJ, Mason EF et al (2011) Cutting edge: distinct glycolytic and lipid oxidative metabolic programs are essential for effector and regulatory CD4+ T cell subsets. J Immunol 186(6):3299–3303. https://doi.org/10.4049/jimmunol.1003613

Article  CAS  PubMed  Google Scholar 

Mitrasinovic OM, Murphy GM Jr (2003) Microglial overexpression of the M-CSF receptor augments phagocytosis of opsonized Abeta. Neurobiol Aging 24(6):807–815. https://doi.org/10.1016/s0197-4580(02)00237-3

Article  CAS  PubMed  Google Scholar 

Monsonego A, Imitola J, Petrovic S, Zota V, Nemirovsky A, Baron R et al (2006) Abeta-induced meningoencephalitis is IFN-gamma-dependent and is associated with T cell-dependent clearance of Abeta in a mouse model of Alzheimer’s disease. Proc Natl Acad Sci USA 103(13):5048–5053. https://doi.org/10.1073/pnas.0506209103

Article  CAS  PubMed  PubMed Central  Google Scholar 

Monsonego A, Nemirovsky A, Harpaz I (2013) CD4 T cells in immunity and immunotherapy of Alzheimer’s disease. Immunology 139(4):438–446. https://doi.org/10.1111/imm.12103

Article  CAS  PubMed  PubMed Central  Google Scholar 

Monsonego A, Zota V, Karni A, Krieger JI, Bar-Or A, Bitan G et al (2003) Increased T cell reactivity to amyloid beta protein in older humans and patients with Alzheimer disease. J Clin Invest 112(3):415–422. https://doi.org/10.1172/JCI18104

Article  CAS  PubMed  PubMed Central  Google Scholar 

Mrdjen D, Pavlovic A, Hartmann FJ, Schreiner B, Utz SG, Leung BP et al (2018) High-dimensional single-cell mapping of central nervous system immune cells reveals distinct myeloid subsets in health, aging, and disease. Immunity 48(2):380–395. https://doi.org/10.1016/j.immuni.2018.01.011

Article  CAS  PubMed  Google Scholar 

Paresce DM, Ghosh RN, Maxfield FR (1996) Microglial cells internalize aggregates of the Alzheimer’s disease amyloid beta-protein via a scavenger receptor. Neuron 17(3):553–565. https://doi.org/10.1016/s0896-6273(00)80187-7

Article  CAS  PubMed