Research group - Annika Karlsson
Through our research we will gain insights into how to achieve optimized treatment of HIV in perinatally infected children, pregnant women, adults, and in HIV-associated cancers. We are the link between immune response and health in treated HIV-infection.
The link between immune response and health in treated HIV-infection
Chronic infection and immunosuppression are important risk factors for many types of cancer. HIV is one chronic infection associated with severe immunosuppression that is only partly reversed by antiretroviral treatment (ART). In an era where HIV-infected individuals require life-long ART to control viral replication it is important to reveal the mechanisms linked to adverse health effects in order to refine therapeutic interventions, especially in pregnant women, children and adolescence. The CD4 and CD8 T cells which is an important part of the adaptive cellular immune system in both cancer and chronic infection becomes highly dysfunctional during an HIV-infection. This process is usually known as T cell exhaustion. In our projects the goal is to gain insights into how to achieve optimized treatment of HIV in perinatally infected children, pregnant women, adults, and in HIV-associated cancers. Thereby leading the way to better clinical outcomes in HIV infected and uninfected patients.
1. HIV-specific T cell pathogenesis and immune exhaustion
In this research project, we aim to identify intra and extracellular determinants for optimal T cell function and reconstitution in an immunosuppressed host. Antigen-specific T cells that are key components for an effective immune response against viral and bacterial infection and in controlling tumor growth. CD4 T cells coordinate immunity and the CD8T cells exert antiviral effector functions. The central role of CD4 T cells in host protection is particularly apparent after HIV infection, where depletion of the CD4 T helper cell arm contributes to T cell exhaustion (Figure 1). A deeper knowledge of the causes and consequences of immune exhaustion and immune recovery, can be used to decrease morbidity and mortality in HIV-infected children and adults.
2. Biomarkers affecting immune recovery and health in perinatally HIV-infected children and pregnant women
Each year 60-80 children are born to HIV-infected women in Sweden. The numbers have increased in recent years. In the pregnant woman, ART is essential to control viral replication and prevent mother to child transmission, but reported adverse effects are worrying and include pre-eclampsia, preterm birth, low bodyweight.
Despite great success of early initiated ART in reducing infant mortality, HIV-infected children are still affected by a number of HIV-inflicted issues to a greater extent than adults. Rates of virological failure associated with ART-resistance are higher than in young adults in Europe, CD4 T cell recovery is lower despite viral suppression and vaccination responses are impaired.
The optimal ART of HIV-positive individuals during pregnancy, childhood, and adolescence with regard to adverse effects during pregnancy, viral control, immune function, and its long-term effects on morbidity and mortality remains unknown. The results from this project will help to improve the guidelines for treatment selection of pregnant HIV-positive women and children, as well as increase our knowledge about current and past treatment options
3. The role of virus-specific T cell exhaustion in human cancer
HIV is together with human papillomavirus (HPV), Hepatitis B and C viruses (HBV and HCV), and Helicobacter pylori (H. pylori) among the chronic infections related to cancer. In 2012 approximately 195,000 of new cancer cases in Europe were related to chronic infections. Immunosuppression is an important risk factor for many types of cancer. To increase the survival rate in invasive cancer novel immune-based treatment options needs to be developed. To obtain more efficient therapy options for cancer in different stages of development, combinational therapies using immune checkpoints inhibitors to enhance antigen-specific T cell responses are a promising option. Our research goal is to combine clinical, immunological, and molecular biology methodology with bioinformatics to characterize the molecular mechanisms of HIV- and HPV-specific T cells in human cancer affecting disease progression and health (Figure 2). Our long-term goal is to gain insight towards better cancer treatment and prevention of cancer progression
Research group leader
Carina Pérez, 2011
Carina defended her PhD in 2011. Part of her doctoral research was carried out a Gladstone Institutes, University of California, San Francisco together with Prof Douglas Nixon. After her graduation, Carina started up the non-profit company DANSPIRATION (http://www.danspiration.se) in which she through dance aim to inspire, communicate, inform and integrate. Today, Carina is the head of Biosafety at Vironova AB, Stockholm, Sweden.
Melissa Norström, 2012
Melissa defended her PhD in 2012. Part of her doctoral research was carried out at Department of Pathology of the University of Florida College of Medicine together with Prof Marco Salemi. After this she continued as a postdoctoral fellow at Centre for Allogeneic Stem Cell Transplantation (CAST), Department of Oncology and Pathology, KI, Stockholm, Sweden.
Marcus defended his PhD in 2014. He was awarded the Sven Gards stipendium for the best PhD thesis in virologi at KI during 2014. He also received international postdoc grant from the Swedish research council 2014 and joined Dr. Michael Betts lab, Department of Microbiology, University of Pennsylvania, PA, USA. In 2017 he returned to KI, Department of Medicine as an Assistant Professor and became group leader in 2019 https://orcid.org/0000-0003-0633-1719.
Johanna Taurianen, 2016
Johanna defended her PhD in 2016. Since then she has continued her studies on viral-associated CD8 and NK cell responses as a Postdoctoral Fellow in Dr. Jonas Klingström group, Department of Medicine, Center for Infectious Medicine – CIM, Karolinska Institutet.
2013: Karin Sundström, PhD student, MTC, Karolinska Institute, Stockholm.
2012: Charlotte Hedskog, MTC, Karolinska Institute, Stockholm
2010: Annica Lindqvist. PhD student, Karolinska Institute, Stockholm
2009: Andreas Boberg, PhD student, MTC, Karolinska Institute, Stockholm
Leda Parham, 2013
Leda defended her licentiate in 2013. She was part of a SIDA supported collaborative project between Karolinska Institutet and University of Honduras headed by me. Today she is working as a teacher and staff scientist at the Department of microbiology, University of Honduras.
2002: Piotr Nowak. University of Warszawa, Poland, included in the Karolinska Institute Research Training program (KIRT).
Ole Lund, Professor, Technical University of Denmark, Lyngby, Denmark
Morten Nielsen, Professor, Technical University of Denmark, Lyngby, Denmark
Frederick (Rick) M. Hecht, MD, Professor, University of California, San Francisco, USA
Steven G, Deeks, MD, Professor, University of California, San Francisco, USA
Marco Salemi, PhD, Professor, University of Florida, USA
Lars Navér, MD, PhD Section Manager Neonatal operations, Senior Consultant Neonatology and Pediatrics at Karolinska University Hospital Huddinge.
Karin Pettersson, MD, PhD. Head of obstetrics, Senior Consultant Obstetrics at Karolinska University Hospital.
Anders Thalme, MD. Medical head for the HIV outpatient unit and senior consultant at Division of Infectious Diseases, Karolinska University Hospital, Huddinge
Pär Sparén, MD, Professor, KI and Karolinska University Hospital
Joakim Dillner, MD, Professor, KI and Karolinska University Hospital
ALF Medicine https://forskningsstod.vmi.se/Ansokan/start.asp
Läkare mot AIDS forskningsfond http://www.aidsfond.se/
Annika C Karlsson
Karolinska Institutet, ANA FUTURA,
Division of Clinical Microbiology, Department of Laboratory Medicine
Alfred Nobels Allé 8
141 52 Huddinge
Delayed expression of PD1 and TIGIT on HIV-specific CD8 T-cells in untreated HLA-B*57:01 individuals followed from early infection.
Scharf L, Tauriainen J, Buggert M, Hartogensis W, Nolan DJ, Deeks SG, et al
J. Virol. 2020 Apr;():
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 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
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
T-bet and Eomes are differentially linked to the exhausted phenotype of CD8+ T cells in HIV infection.
Buggert M, Tauriainen J, Yamamoto T, Frederiksen J, Ivarsson MA, Michaëlsson J, et al
PLoS Pathog. 2014 Jul;10(7):e1004251
Multiparametric bioinformatics distinguish the CD4/CD8 ratio as a suitable laboratory predictor of combined T cell pathogenesis in HIV infection.
Buggert M, Frederiksen J, Noyan K, Svärd J, Barqasho B, Sönnerborg A, et al
J. Immunol. 2014 Mar;192(5):2099-108
Combination of immune and viral factors distinguishes low-risk versus high-risk HIV-1 disease progression in HLA-B*5701 subjects.
Norström MM, Buggert M, Tauriainen J, Hartogensis W, Prosperi MC, Wallet MA, et al
J. Virol. 2012 Sep;86(18):9802-16
Interdisciplinary analysis of HIV-specific CD8+ T cell responses against variant epitopes reveals restricted TCR promiscuity.
Hoof I, Pérez CL, Buggert M, Gustafsson RK, Nielsen M, Lund O, et al
J. Immunol. 2010 May;184(9):5383-91
Broadly immunogenic HLA class I supertype-restricted elite CTL epitopes recognized in a diverse population infected with different HIV-1 subtypes.
Pérez CL, Larsen MV, Gustafsson R, Norström MM, Atlas A, Nixon DF, et al
J. Immunol. 2008 Apr;180(7):5092-100