Helena Reijonen , Ph.D.
Affiliate Assistant Professor, Immunology

Research Assistant Member, Diabetes Program
Benaroya Research Institute
1201 Ninth Ave Seattle WA 98101
tel: 206-341 1343
fax: 206-223 7638 e-mail:
Email: reijonen@benaroyaresearch.org

Helena Reijonen received her PhD from the University of Turku in Finland in 1994. She did her post-doctoral training in Dr Gerald Nepom’s laboratory, and is currently Research Assistant Member at Benaroya Research Institute.

Description of the projects:

The precise nature of the T lymphocyte response in type 1 diabetes, and the regulation of this response, is one of the key barriers to a full understanding of autoimmune predisposition, disease progression, and the rational design of immunotherapies. Our research projects aim to improve the understanding of  diversity of the immune cell repertoire responsible for the destruction or protection of insulin-producing beta cells.

We focus on the following areas:

1. Identification of T lymphocytes that are relevant for the progression to type 1 diabetes, and understanding the characteristics of these cells. Utilization of MHC class II tetramers allows enumeration and phenotyping of disease specific T cells and monitoring changes in the autoimmune response during the disease progression.  We are also involved in several clinical trials on type 1 diabetes, investigating responses to immunomodulatory therapies aimed at intervention of islet-specific autoimmunity.

2. Recurrence of autoimmunity in type 1 diabetes patients with kidney-pancreas transplants.  Future development of this research area includes strategies to prevent recurrence of autoimmunity and destruction of the transplanted islets in type 1 diabetes patients who have received simultaneous kidney-pancreas (SKP) transplants.  Our follow-up study will define the relationship between islet-specific autoantibodies, autoreactive T lymphocytes, inflammation of the islets, and insulin secretion in these patients.  Our research team is working on characterization of the specificity and phenotype of autoreactive T lymphocytes in blood and occasional biopsy tissues when available.  These studies will provide critical information about the immunological mechanisms regulating recurrence of autoimmunity, persistent T cell memory, and resistance to immunosuppression. 
3. MHC- mediated protection from type 1 diabetes.  The risk to develop type 1 diabetes is associated with the presence of certain MHC class II gene variants, whereas some other MHC class II genes confer dominant protection. The studies of disease regulation will clarify the modifying role of protective MHC class II molecules in the disease progression and explore the underlying mechanism of MHC-mediated protection.

Selected publications:

Reijonen H, Elliott JF, van Endert P, Nepom G. Differential presentation of glutamic acid decarboxylase 65 (GAD65) T cell epitopes among HLA-DRB1*0401 positive individuals. J Immunol 1999(Aug 1); 163: 16674-1681

Reijonen H, Daniels TL, Lernmark A, Nepom GT. GAD65-specific autoantibodies enhance the presentation of an immunodominant T-cell epitope from GAD65. Diabetes 2000; 49(10):1621-1626

Reijonen H, Novak EJ, Kochik S, Heninger A-K, Liu AW, Kwok WW, and Nepom GT. Detection of GAD65 specific T-cells by MHC Class II tetramers in Type 1 diabetes patients and at-risk subjects. Diabetes, 2002; 51:1375-1382

Nepom GT, Buckner JH, Novak EJ, Reichstetter S, Reijonen H, Gebe J, Wang R, Swanson E, Kwok WW. HLA class II tetramers: tools for direct analysis of antigen-specific CD4+ T cells. Arthritis Rheum 2002; 46(1):5-12

Buckner JH, Holzer U, Novak EJ, Reijonen H, Kwok WW, Nepom GT. Defining antigen-specific responses with human MHC class II tetramers. J Allergy Clin Immunol. 2002, 110:199-208

Reijonen H and Kwok WW. Use of HLA class II tetramers in tracking antigen-specific T-cells and mapping of T-cell epitopes. Methods 2003; 29(3):282-8

Gebe JA, Falk BA, Rock KA, Kochik SA, Heninger A-K, Reijonen H, Kwok WW and Nepom GT. MHC-peptide recognition by self-antigen specific CD4+ T-cells is a low avidity interaction. Eur J Immunol 2003; 33(5):1409-17

Reijonen H, Kwok WW and Nepom GT. Detection of CD4+ autoreactive T-cells in T1D using HLA class II tetramers. NYAS 6th IDS: Immunology in Diabetes II, Ann Ny Acad Sci 2003, 1005:82-87

Mallone R, Kochik SA, Laughlin EM, Gersuk VH, Reijonen H, Kwok WW, Nepom GT. Differential recognition and activation thresholds in human autoreactive GAD-specific T-cells. Diabetes 2004; 53(4): 971-7

Reijonen H, Heninger A-K, Laughlin EM, Kochik SA, Falk BA, Kwok WW, Greenbaum C and Nepom GT. GAD65 specific CD4+ T cells with high antigen avidity are prevalent in peripheral blood of Type 1 diabetes patients. Diabetes 2004, 53:1987-94

Gebe JA, Masewicz SA, Kochik SA, Reijonen H and Nepom GT. Inhibition of altered peptide ligand-mediated antagonism of human GAD65-responsive CD4+ T cells by non-antagonizable T cells. Eur J Immunol 2004; 34: 3337-3345

Reijonen H and Concannon P. Genetics of Type 1 Diabetes. In Joslin’s Diabetes Mellitus, New York, Lippincott, Williams & Wilkins, 2005, p. 355-370.

Mallone R, Kochik SA, Reijonen H, Carson B, Ziegler SF, Kwok W and Nepom GT. Functional avidity directs T-cell fate in autoreactive CD4+ T-cells. Blood 2005; 106:2798-2805

Öling V, Marttila J, Ilonen J, Kwok WW, Nepom GT, Knip M, Simell O and Reijonen H. GAD65- and Proinsulin-Specific CD4+ T-Cells Detected by MHC Class II Tetramers in Peripheral Blood of Type 1 Diabetes Patients and At-Risk Subjects. J Autoimmunity 2005, Nov; 25(3):235-43

Yang J, Danke NA, Berger D, Reichstetter S, Reijonen H, Greenbaum C, Pihoker C, James EA and Kwok WW. Islet-specific glucose-6-phosphatase catalytic subunit-related protein-reactive CD4+ T cells in human subjects. J Immunol 2006; 176(5):2781-9

Martin-Pagola A, Sisino G, Allende G, Dominguez-Bendala J, Gianani R, Reijonen H, Nepom GT, Ricordi C, Ruiz P, Sageshima J, Ciancio G, Burke GW, Pugliese A. Insulin protein and proliferation in ductal cells in the transplanted pancreas of patients with type 1 diabetes and recurrence of autoimmunity. Diabetologia. 2008 Oct;51(10):1803-13. PMID: 18696047

Updated 8/25/09