Th1 responses to beta-amyloid in young humans convert to regulatory IL-10 responses in Down syndrome and Alzheimer's disease

Loewenbrueck, Kai F.; Tigno-Aranjuez, Justine T.; Boehm, Bernhard O.; Lehmann, Paul V.; Tary-Lehmann, Magdalena

doi:10.1016/j.neurobiolaging.2008.09.007

« Previous Next »Neurobiology of Aging
Volume 31, Issue 10 , Pages 1732-1742, October 2010

Th1 responses to beta-amyloid in young humans convert to regulatory IL-10 responses in Down syndrome and Alzheimer's disease

Kai F. Loewenbrueck
- Department of Pathology, Case Western Reserve University School of Medicine, Cleveland, OH 44106, USA
- Division of Endocrinology, Department of Medicine, University Hospital Ulm, 89081 Ulm, Germany
- Department of Neurology, University Hospital “Carl Gustav Carus”, Dresden University of Technology, 01307 Dresden, Germany
- Corresponding author at: Department of Pathology, Wolstein Research Building, Room # 5128, Case Western Reserve University, 10900 Euclid Ave., Cleveland, OH 44106, USA. Permanent address: Department of Neurology, University Hospital “Carl Gustav Carus”, Dresden University of Technology, 01307 Dresden, Germany. Tel.: +49 351 458 2532.
Justine T. Tigno-Aranjuez
- Department of Pathology, Case Western Reserve University School of Medicine, Cleveland, OH 44106, USA
- Tel.: +1 216 368 1365; fax: +1 216 368 1357.
Bernhard O. Boehm
- Division of Endocrinology, Department of Medicine, University Hospital Ulm, 89081 Ulm, Germany
- Tel.: +49 731 500 44504; fax: +49 731 500 44506.
Paul V. Lehmann
- Department of Pathology, Case Western Reserve University School of Medicine, Cleveland, OH 44106, USA
- Tel.: +1 216 368 1365; fax: +1 216 368 1357.
Magdalena Tary-Lehmann
- Department of Pathology, Case Western Reserve University School of Medicine, Cleveland, OH 44106, USA
- Tel.: +1 216 368 1298; fax: +1 216 368 1357.

Received 9 November 2007; received in revised form 22 August 2008; accepted 16 September 2008. published online 08 December 2008.

Abstract

Aβ_1–42-specific antibodies and T-cell proliferation point to the existence of a memory response to Aβ_1–42 in humans. Using ELISPOT, we studied Aβ_1–42-specific T cells in individuals of various ages, and in subjects with Trisomy 21 or Alzheimer's disease. We show for the first time that Aβ_1–42-specific Th1-type T-cell memory is present in young humans, producing high levels of IFN-γ and IL-2. With increasing age, the production of IFN-γ and IL-2 decreases but is not discontinued in healthy subjects and is accompanied by a sharp rise in CD4⁺ T-cell-derived regulatory IL-10 production. In contrast, individuals with Trisomy 21 and with Alzheimer's disease produce IL-10 only in the absence of any effector cytokine. This signifies a switch from a Th1 effector to an IL-10 mediated regulatory response.

Abbreviations: Aβ_1–42, beta-amyloid 1–42, APCs, antigen presenting cells, APP, amyloid precursor protein, CFA, complete Freund's adjuvant, CNS, central nervous system, CRP, C-reactive protein, CpG, cytidine-phosphate-guanosine, EAE, experimental allergic encephalomyelitis, i.c., intracutaneous, IFA, incomplete Freund's adjuvant, IFN, interferon, IL, interleukin, KLH, keyhole limpet hemocyanin, MBP, myelin basic protein, MMSE, mini mental state exam, MS, multiple sclerosis, OxLDL, oxidized low density lipoprotein, PBMC, peripheral blood mononuclear cells, PLP, proteolipid protein, PTX, pertussis toxin, sAP, serum amyloid protein, Th, T helper, Treg, T regulatory, TT, tetanus toxoid