Marcus Buggert group - T cell immunity to viral infections and cancer

We conduct innovative studies of cell-mediated immunity in health, cancer and viral disease.

The Marcus Buggert research group. Photo: Private

About our research

Our group conducts research on cell-mediated immunity. More specifically, we are interested in understanding how memory T cells recognize and eliminates viral infections and tumors. Much of our research is focused on the CD8+ T cell arm of cell-mediated immunity. CD8+ T cells are absolutely critical for immune control of most viral infections, and also represent a major cellular component of immune therapies that have entirely revolutionized cancer care. However, many still view CD8+ T cells solely as killer T cells eliminating virus-infected or tumor cells based on concepts from studies of peripheral blood.

Emerging data from us and others have demonstrated that most memory CD8+ T cells in human tissues are resident cells with limited recirculation capacity back to peripheral blood. These CD8+ T cells in tissues show differential transcriptional, epigenetic, and functional programming from circulating CD8+ T cells. This is important, as these data indicate that previous studies in blood have largely failed to capture how memory CD8+ T cells function and potentially control human diseases in tissues.

Studies of different aspects of human memory T cell biology

Our group use cutting-edge bulk- and single-cell technologies including 30-parameter flow cytometry, gene-expression, RNA-seq, ATAC-seq, TCR-seq and proteomics analysis to dissect the heterogeneity and function of memory T cell immunity. Through these platforms, we study different aspects of human memory T cell biology, with an overall aim toi) study the heterogeneity of circulating and resident memory T cells in human organ donors, ii) identify alternative functions of memory T cells in human tissues, and iii) understand how memory T cells maintain control of tumors and viral infections, such as HIV and SARS-CoV-2.

Illustration, research
Illustration of project outlines in the group.

Collaborations

The research group's lab is located in a vibrant research environment at the Center for Infectious Medicine (CIM) in the top modern ANA Futura laboratories. Here, we function in close conjunction with other research groups at CIM, and also collaborate with clinicians and surgeons at the Karolinska University Hospital Huddinge to receive valuable samples. We also collaborate with other researchers at Karolinska Institutet and Science for Life laboratories in Sweden, as well with leading researchers in our field from universities in Denmark, Germany, Great Britain, Spain, and USA.

Group leader

Marcus Buggert

Group leader, Assistant Professor, PhD

Marcus conducted both Master studies in Biomedicine and his PhD at KI. After post-doctoral studies at University of Pennsylvania, he came back to KI where he joined CIM as an Assistant Professor and Principal Investigator.

Marcus Buggerts research is focused on studies of human circulating and resident memory CD8+ T cell functions in health, cancer and HIV infection. Marcus loves sport (more watching than executing) and spending time with his family and friends.

Group members

Olga Rivera Ballesteros

PhD student

Olga received her MSc in Immunology and Inflammation in 2019 at University of Copenhagen, where she studied the immunomodulatory role of mesenchymal stem cells. At CIM her work is focused on understanding the heterogeneity and functions of follicular CD8+ T cells, with attention to HIV and cancer immunity. Olga enjoys hiking, practicing yoga, photography, and good conversations with friends. 

Curtis Cai

PhD

Curtis received his PhD in Pathology in 2021 at the University of New South Wales, Australia. There he studied T cell responses of human viral infections and immunotherapy using, what was at the time, the emerging technique of scRNA-seq. Now at CIM, his work is applying lab- and computational single-cell multi-omics to study vaccine responses and tissue-specific distribution of memory T cells. Don’t be surprised to find Curtis outdoors making the most of the splendid Swedish summers and white winters. 

Joshua Lange

PhD, Post doc

Joshua received his PhD in Immunology in 2020 at the University of Otago, New Zealand. His research was focused on the developing cancer therapies that exploited the immunomodulating properties of innate-like T cells. At CIM, his work involves understanding the specific CD8+ T cell responses responsible for successful immune checkpoint blockade therapy. In his spare time, you will find Joshua out enjoying a drink with his friends, playing video games and cooking traditional Filipino food.

Julia Niessl

PhD, Post doc

Julia received her PhD in Virology and Immunology in 2020 at the Université de Montréal, where she studied the modulation of HIV-specific T cell responses during standard antiretroviral therapy and immunotherapy. At CIM, her work is focused on understanding the distribution, functionality, clonality and heterogeneity of virus-specific tissue-resident memory T cells in various human donor organs. Julia enjoys reading a good book, having beers with friends, watching American football and travelling all over the world. 

Takuya Sekine

PhD, Post doc

Tak received his PhD in 2016 from Imperial College London. His work is focused on characterizing exhausted and tumor infiltrating CD8+ T cells in disease conditions, such as Langerhans cell histiocytosis. He is also studying the functional heterogeneity of CD8+ T cells residing in lymph nodes and other secondary lymphoid organs. In his spare time, Tak enjoys exercise (running, swimming), playing football and exploring new coffee spots.

Thomas Müller

PhD, Postdoc

Thomas received his PhD in Experimental Medicine in 2021 at the Technical University in Munich. There he studied the biology of the T cell receptor (TCR) and developed CRISPR/Cas9-mediated orthotopic TCR replacement to generate improved TCR-edited T cells for immunotherapy. At CIM, Thomas investigates the functional role of tissue-resident memory T cells in the tumor microenvironment, ultimately aiming at translation into novel strategies for the treatment of solid tumors. In his spare time, he loves being outdoors to ride his bike, swim, or hike mountains. He also enjoys cooking, especially when it’s accompanied by good friends and a drink.

Open positions 

We are constantly looking for talented post docs with an ambition to explore new and unique aspects of human T cell immunology, tissue immunology, and related questions.

If interested, please contact Group leader Marcus Buggert

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Research support

  • The Swedish Research Council (Vetenskapsrådet) 
     
  • Knut and Alice Wallenberg Foundation (KAW) 
     
  • The Swedish Cancer Society (Cancerfonden) 
     
  • Åke Wiberg Stiftelse 
     
  • Jeanssons Stiftelser 
     
  • The Swedish Childhood Cancer Foundation (Barncancerfonden) 
     
  • The Swedish Heart Lung Foundation (Hjärt-Lungfonden) 
     
  • The Swedish Society of Medicine (Svenska Läkaresällskapet) 
     
  • Center for Innovative Medicine
     
  • EMBO

 

Selected publications

2020

Deciphering the ins and outs of SARS-CoV-2-specific T cells.
Perez-Potti A, Lange J, Buggert M
Nat Immunol 2021 01;22(1):8-9

The Identity of Human Tissue-Emigrant CD8+ T Cells.
Buggert M, Vella LA, Nguyen S, Wu VH, Chen Z, Sekine T, Perez-Potti A, Maldini CR, Manne S, Darko S, Ransier A, Kuri-Cervantes L, Japp AS, Brody IB, Ivarsson MA, Gorin JB, Rivera-Ballesteros O, Hertwig L, Antel JP, Johnson ME, Okoye A, Picker L, Vahedi G, Sparrelid E, Llewellyn-Lacey S, Gostick E, Sandberg JK, Björkström N, Bar-Or A, Dori Y, Naji A, Canaday DH, Laufer TM, Wells AD, Price DA, Frank I, Douek DC, Wherry EJ, Itkin MG, Betts MR
Cell 2020 Dec;183(7):1946-1961.e15

The known unknowns of T cell immunity to COVID-19.
Karlsson AC, Humbert M, Buggert M
Sci Immunol 2020 11;5(53):

Robust T Cell Immunity in Convalescent Individuals with Asymptomatic or Mild COVID-19.
Sekine T, Perez-Potti A, Rivera-Ballesteros O, Strålin K, Gorin JB, Olsson A, Llewellyn-Lacey S, Kamal H, Bogdanovic G, Muschiol S, Wullimann DJ, Kammann T, Emgård J, Parrot T, Folkesson E, , Rooyackers O, Eriksson LI, Henter JI, Sönnerborg A, Allander T, Albert J, Nielsen M, Klingström J, Gredmark-Russ S, Björkström NK, Sandberg JK, Price DA, Ljunggren HG, Aleman S, Buggert M
Cell 2020 10;183(1):158-168.e14

TOX is expressed by exhausted and polyfunctional human effector memory CD8+ T cells.
Sekine T, Perez-Potti A, Nguyen S, Gorin JB, Wu VH, Gostick E, et al
Sci Immunol 2020 Jul;5(49):

Elite control of HIV is associated with distinct functional and transcriptional signatures in lymphoid tissue CD8+ T cells.
Nguyen S, Deleage C, Darko S, Ransier A, Truong DP, Agarwal D, et al
Sci Transl Med 2019 12;11(523):

2019

CD8+ T cells in lymphoid tissues exhibit distinct functional and transcriptional signatures that associate with elite control of HIV.
Nguyen S, Deleage C, Darko S, Ransier A, Truong D, Agarwal D, Sada Japp A Wu, VH, Kuri-Cervantes L, Abdel-Mohsen M, Del Rio Estrada PM, Ablanedo-Terrazas Y, Gostick E, Price DA, Hoxie JA, Naji A, Reyes-Terán G, Estes JD, Douek DC, Deeks SG, Buggert M*, Betts MR*.
Accepted in Science Translational Medicine

T follicular helper cells in human efferent lymph retain lymphoid characteristics.
Vella LA, Buggert M, Manne S, Herati RS, Sayin I, Kuri-Cervantes L, et al
J. Clin. Invest. 2019 07;129(8):3185-3200

Everything in its right place: resident memory CD8+ T cell immunosurveillance of HIV infection.
Buggert M, Japp AS, Betts MR
Curr Opin HIV AIDS 2019 Mar;14(2):93-99

2018

Identification and characterization of HIV-specific resident memory CD8+ T cells in human lymphoid tissue.
Buggert M, Nguyen S, Salgado-Montes de Oca G, Bengsch B, Darko S, Ransier A, et al
Sci Immunol 2018 06;3(24):

Spatial distribution and function of T follicular regulatory cells in human lymph nodes.
Sayin I, Radtke AJ, Vella LA, Jin W, Wherry EJ, Buggert M, et al
J. Exp. Med. 2018 06;215(6):1531-1542

Limited immune surveillance in lymphoid tissue by cytolytic CD4+ T cells during health and HIV disease.
Buggert M, Nguyen S, McLane LM, Steblyanko M, Anikeeva N, Paquin-Proulx D, et al
PLoS Pathog. 2018 04;14(4):e1006973

Human MAIT cells exit peripheral tissues and recirculate via lymph in steady state conditions.
Voillet V, Buggert M, Slichter CK, Berkson JD, Mair F, Addison MM, et al
JCI Insight 2018 04;3(7):

Human Immunodeficiency Virus Type-1 Elite Controllers Maintain Low Co-Expression of Inhibitory Receptors on CD4+ T Cells.
Noyan K, Nguyen S, Betts MR, Sönnerborg A, Buggert M
Front Immunol 2018 ;9():19

Human Immunodeficiency Virus-Infected Women Have High Numbers of CD103-CD8+ T Cells Residing Close to the Basal Membrane of the Ectocervical Epithelium.
Gibbs A, Buggert M, Edfeldt G, Ranefall P, Introini A, Cheuk S, et al
J. Infect. Dis. 2018 07;218(3):453-465

2017

HIV-Specific CD8+ T Cells Exhibit Reduced and Differentially Regulated Cytolytic Activity in Lymphoid Tissue.
Reuter MA, Del Rio Estrada PM, Buggert M, Petrovas C, Ferrando-Martinez S, Nguyen S, et al
Cell Rep 2017 Dec;21(12):3458-3470

T-bet+ B cells are induced by human viral infections and dominate the HIV gp140 response.
Knox JJ, Buggert M, Kardava L, Seaton KE, Eller MA, Canaday DH, et al
JCI Insight 2017 Apr;2(8):

Perturbed CD8+ T cell TIGIT/CD226/PVR axis despite early initiation of antiretroviral treatment in HIV infected individuals.
Tauriainen J, Scharf L, Frederiksen J, Naji A, Ljunggren HG, Sönnerborg A, et al
Sci Rep 2017 01;7():40354

Combined immunodeficiency and Epstein-Barr virus-induced B cell malignancy in humans with inherited CD70 deficiency.
Abolhassani H, Edwards ES, Ikinciogullari A, Jing H, Borte S, Buggert M, et al
J. Exp. Med. 2017 01;214(1):91-106