My long term research interests involve the development of a comprehensive understanding on the role of T cells in the initiation and maintenance of human and experimental autoreactivity. As a Fulbright scholar, in the lab of Prof. Dr. Salvatore Albani, I focused on distilling the mechanisms of epitope-specific immune therapy in rheumatoid arthritis (RA). As a predoctoral student under the supervision of Dr. Femke van Wijk and Prof. Dr. Berent Prakken, my research focused on the dynamics of T cell reconstitution in children thymectomized within their first month of life (ref. 1) and after stem cell transplantation for autoimmune diseases in humans and murine models (ref. 2). My findings identified a novel functional marker for recent thymic emigrants and significantly altered the concept of naïve T cells as developmentally synchronized and relatively homogeneous cell population and incited the need for a revision (ref. 3). The necessity of T cell help for the development of human B cell autoreactivity was further investigated in close collaboration with the Weizmann Institute of Science (Rehovot, Israel, Prof. Irun Cohen) (ref. 4). Overall, this has skilled me in several clinical autoimmune diseases as well as techniques in cellular immunology in humans and mice.
My current research (supported by a Marie Curie Global Fellowship) builds logically on my prior work on the specific role of T cells in the development of B cell autoreactivity.
Contributions to Science (NIH style)
1. The role of the thymus in the generation of new T cells is well known, but neonatal thymectomy frequently occurs during open heart surgery to get a clear view on the heart. These studies emphasized that the neonatal thymectomy resulted in altered T cell function and homeostasis, induced the development of B cell autoreactivity, but more importantly I found a signatory functional marker that identified recent thymic emigrants. Furthermore, these findings significantly altered the concept of naïve T cells as developmentally synchronized and relatively homogeneous cell population and incited the need for a revision (review in Nat Rev Imm).
– van den Broek T, Madi A, Delemarre EM, Schadenberg AWL, Tesselaar K, Borghans JAM, Nierkens S, Redegeld FA, Otten HG, Rossetti M, Albani S, Sorek R, Cohen IR, Jansen NJG, van Wijk F. (2017)
Human neonatal thymectomy induces altered B-cell responses and autoreactivity.
European journal of immunology. 47(11): 1970-1981. (PMID: 28691750)
– van den Broek T, Delemarre EM, Janssen WJ, Nievelstein RA, Broen JC, Tesselaar K, Borghans JA, Nieuwenhuis EE, Prakken BJ, Mokry M, Jansen NJ, van Wijk F. (2016)
Neonatal thymectomy reveals differentiation and plasticity within human naive T cells.
The Journal of clinical investigation. 126(3): 1126-36. (PMID: 26901814, PMCID: PMC4767338)
– Schadenberg AW, van den Broek T, Siemelink MA, Algra SO, de Jong PR, Jansen NJ, Prakken BJ, van Wijk F. (2014)
Differential homeostatic dynamics of human regulatory T-cell subsets following neonatal thymectomy.
The Journal of allergy and clinical immunology. 133(1):277-80.e1-6. (PMID: 24139831)
2. I assessed the immunological mechanisms of different strategies in the treatment of Rheumatoid arthritis. While different successful treatment regimens, such as Disease Modifying Anti-Rheumatic Drugs (DMARDs) and biologics are available for the treatment of rheumatoid arthritis, they need to be taken continuously, as clinical control fades with withdrawal of therapy. With this research we provided further immunological insight in treatment options that could change the autoreactive response (immune therapy) and could even cure rheumatoid arthritis without the need of further medication. By providing evidence in both murine and human autoimmune disease this work has changed the perception of how stem cell transplantation could cure autoimmune disease, and has been highlighted in both Blood (PMID: 26744435) and Nat Rev Rheum (PMID: 26526646).
– Delemarre EM*, van den Broek T*, Mijnheer G, Meerding J, Wehrens EJ, Olek S, Boes M, van Herwijnen MJ, Broere F, van Royen A, Wulffraat NM, Prakken BJ, Spierings E, van Wijk F. (*contributed equally) (2016)
Autologous stem cell transplantation aids autoimmune patients by functional renewal and TCR diversification of regulatory T cells.
Blood; 127(1):91-101. (PMID: 26480932)
– Delemarre EM*, Roord ST*, van den Broek T, Zonneveld-Huijssoon E, de Jager W, Rozemuller H, Martens AC, Broere F, Wulffraat NM, Glant TT, Prakken BJ, van Wijk F. (2014)
Autologous stem cell transplantation restores immune tolerance in experimental arthritis by renewal and modulation of the Teff cell compartment.
Arthritis & rheumatology; 66(2):350-6. (*contributed equally) (PMID: 24504807)
– Koffeman EC, Genovese M, Amox D, Keogh E, Santana E, Matteson EL, Kavanaugh A, Molitor JA, Schiff MH, Posever JO, Bathon JM, Kivitz AJ, Samodal R, Belardi F, Dennehey C, van den Broek T, van Wijk F, Zhang X, Zieseniss P, Le T, Prakken BA, Cutter GC, Albani S. (2009)
Epitope-specific immunotherapy of rheumatoid arthritis: clinical responsiveness occurs with immune deviation and relies on the expression of a cluster of molecules associated with T cell tolerance in a double-blind, placebo-controlled, pilot phase II trial.
Arthritis and rheumatism; 60(11):3207-16. (PMID: 19877047)
3. Within a certain type/group of autoimmune disease further heterogeneity is present and results in differences in disease severity, prognosis and response to therapy. These studies identified the evolution of biomarkers in rheumatoid arthritis and directly contributed to the better identification of homogenous groups within juvenile idiopathic arthritis via the use of biomarkers and clinical characteristics.
– van den Broek T, Hoppenreijs E, Meerding J, Scholman R, Otten HG, Swart JF, Martini A, Prakken B, de Jager W. (2015)
Cytokine profiling at disease onset: support for classification of young antinuclear antibody-positive patients as a separate category of juvenile idiopathic arthritis.
Annals of the rheumatic diseases. 74(2):470-2. (PMID: 25384964)
– van den Broek T, Tesser JR, Albani S. (2008)
The evolution of biomarkers in rheumatoid arthritis: from clinical research to clinical care.
Expert opinion on biological therapy. 8(11):1773-85. (PMID: 18847311)