Cellular Immunology
Advancing paediatric immunology and disease prevention.
The Cellular Immunology group investigates the human immune system to identify immune biomarkers of disease in children. By understanding how immune responses develop and malfunction early in life, our research aims to inform the development of new vaccines, treatments, and immunotherapies to prevent and manage childhood disease.
The immune system changes significantly with age, and children are particularly vulnerable to infections and immune‑mediated conditions in early life. Studying these developmental changes is essential for improving outcomes across a wide range of paediatric diseases.
Understanding immune responses in childhood disease
Our research focuses on how the immune system in children responds to infectious diseases such as Group A Streptococcus and Tuberculosis, as well as conditions where the immune system attacks its own tissues.
Key areas of investigation include:
- Autoimmune disease, including Type 1 diabetes
- Transplant immunology, particularly immune responses following heart transplantation
- Neuromuscular disorders, such as muscular dystrophy, where immune dysfunction contributes to disease progression
By examining immune function across these conditions, we seek to understand why immune responses differ in children and how these responses contribute to disease.
Translating immunology research into therapies and vaccines
The main aim of our research is to understand the role of the human immune system in these paediatric diseases and to exploit this knowledge to develop new vaccines and therapies to prevent childhood diseases.
T Cells and the developing immune system
Thecentral focus of our work is the study of white blood cells called T cells, which are crucial for the survival of all humans.
Understanding how T cells develop, adapt, and sometimes malfunction across the lifespan is key to improving treatments for infection, autoimmune disease, transplant rejection, and chronic inflammatory conditions in children.
Group Leaders
Group Members
Our projects
Characterisation of the human immune system in children and adolescents
The immune system is not static, it grows, adapts, and evolves from infancy through adolescence, laying the foundation for health across a lifetime. Yet a child’s immune systems remain one of the least understood areas of human biology, largely owing to lack of research into understanding the immune landscape in children.
Advances in studying the human immune system using technologies such as high-dimensional flow cytometry and RNA-sequencing are transforming our understanding of the immune system in children. By enabling the simultaneous measurement of hundreds of immune cells from very small blood volumes, these technologies provide an extraordinary view of how the immune system develops in health and how it becomes disrupted in disease.
Through this approach, we aim to redefine why a child’s immune system is more prone to disease and address critical gaps in paediatric immunology. Our work will accelerate biomarker discovery that can guide earlier diagnosis of diseases, better monitoring, and more precise treatments for children.
To date, we have generated detailed immune reference maps that capture how the human immune system develops from early childhood through to adolescence. By defining a healthy immune system, these maps provide an essential baseline that will allow us to determine how the immune system changes in the context of disease such as infection. This resource enables clearer distinction between healthy immune development and early signs of immune dysfunction, supporting more accurate interpretation of paediatric immune responses across both research and clinical settings.
Furthermore, our research is designed to move beyond discovery by establishing clear pipelines that translate immune insights into clinically meaningful tools. By integrating high-dimensional immune profiling with robust analytical frameworks, we aim to validate immune markers that can be applied in clinical studies and future diagnostic workflows. This approach bridges the gap between complex immunological data and real-world paediatric care.
Understanding the breakdown of the immune system in children diagnosed with Type I Diabetes
Type 1 Diabetes (T1D) is driven by immune-mediated destruction of pancreatic beta cells, yet the precise immune alterations in children at different disease stages remain incompletely understood.
Using high-dimensional immune profiling, we investigate changes in hundreds of immune populations, and regulatory networks in children with T1D. By comparing these profiles to age-matched healthy immune references, we aim to identify immune signatures associated with disease onset and progression. This work seeks to support earlier detection of T1D, improved disease monitoring, and the development of immune-targeted therapeutic strategies to prevent destruction of pancreatic beta cells.
Exploring the dysfunctional immune system in children with Muscular Dystrophy
Muscular Dystrophy is increasingly recognised as not only a genetic muscle disorder but also a condition influenced by chronic immune activation and inflammation.
Our research examines systemic immune alterations in affected children using deep immune profiling approaches. By defining how immune cell subsets and inflammatory pathways are altered, we aim to clarify the contribution of immune dysregulation to disease progression. These findings will inform the development of adjunct immunomodulatory therapies, improve patient stratification in clinical trials and prevent muscle degradation in kids affected by muscular dystrophy.
Preventing heart transplant rejection in children
Despite advances in transplantation medicine, immune-mediated rejection of solid organ transplants remains a major challenge in paediatric heart transplant recipients. Following heart transplantation, a child must return to the Royal Children’s Hospital to have a series of biopsies taken directly from the transplanted heart to ensure the body is not rejecting the organ. This is invasive and enormously burdensome for the families.
Our research analyses the blood of heart transplant recipients and profiles the body’s immune system to identify immune biomarkers associated with rejection and long-term graft outcomes. By integrating immune phenotyping with clinical data, we aim to develop a minimally invasive assay that requires a simple blood test, instead of heart biopsies to detect and prevent transplant rejection. Our work aims to provide more personalised immunosuppressive treatment of children after transplantation, ensuring a long and happy life.
Examine the role of unconventional T cells in Group A Streptococcus infection
Group A Streptococcus (GAS) is a human-specific bacterial pathogen that infects more than half a billion people worldwide each year and causes over 500,000 deaths. Despite its enormous global impact, GAS remains difficult to control using conventional public health measures. As a result, the World Health Organization has identified the development of a protective vaccine against GAS as a top global health priority.
A major barrier to effective vaccine design is our limited understanding of how the human immune system responds to GAS infection. Our previous work has revealed that so-called unconventional T cells play a critical role in shaping immunity to GAS, highlighting an important and previously underappreciated aspect of host defence. In this project, we aim to define how these unconventional T cells influence protection against GAS infection and to explore how their unique properties can be harnessed to inform the design of a next-generation GAS vaccine. To achieve this, we combine cutting-edge approaches including high-dimensional spectral flow cytometry, advanced human organoid culture systems, and the world’s only active human challenge model for GAS infection. Together, these tools allow us to study human immune responses to GAS with unprecedented depth, helping to inform future vaccine design and improve global health outcomes.
Investigate the role of lipid specific white blood T cells in Tuberculosis.
Tuberculosis is caused by an infection with the bacterium Mycobacterium tuberculosis. Despite a vaccine to Tuberculosis and the use of antibiotics, Tuberculosis kills more than 1.5 million people per year and is the number one cause of death caused by an infectious pathogen. Clearly, greater efforts are needed to prevent serious disease and death caused by Tuberculosis.
This research project focuses on understanding the role of CD1 restricted T cells in recognising lipid molecules from Mycobacterium tuberculosis. Our research aims to understand how we can boost the human immune response to lipid antigens and improve vaccine strategies to help eradicate Mycobacterium tuberculosis in humans.
Understanding the development of human unconventional T cells to develop new immunotherapies to prevent cancer and microbial resistant infections
Team members on this project: Dr. Louis Perriman, Jordyn Reinecke (PhD candidate), Imogen Ryan (Honors candidate), Don Srivijitchoke (Volunteer).
Our immune system protects us from disease such as cancer using specialised cells called T cells. Before T cells can do their job, they must undergo a carefully controlled development process in a specialised organ called the thymus.
While most people would be familiar with “conventional” T cells, there is also a group of T cells called unconventional T cells, which include γδ T cells, mucosal associated invariant T cells (MAIT), and natural killer T (NKT) cells. These cells are unique in that they can respond more rapidly to disease compared to conventional T cells. Interestingly, having greater numbers of unconventional T cells leads to better disease outcomes. Despite their potency, little is known about how unconventional T cells are developed in the thymus.
In collaboration with Prof. Igor Konstantinova, a world-leading paediatric surgeon, our team has access to thymus tissue donated from children underdoing heart surgery at the Royal Children’s Hospital. This rare access has provided invaluable insight into unconventional T cell development and has already led to several high impact discoveries (doi:10.1038/ni.3565, 10.1126/sciimmunol.aay6039, 0.1126/sciimmunol.abo4365). However, studying donated thymus tissue alone has limitations, as it cannot be experimentally manipulated to test which factors are truly essential for unconventional T cell development. This challenge is compounded by the fact that some unconventional T cell populations do not exist in mice, the most commonly used animal model in immunology research.
A major breakthrough has come from Prof. Ed Stanley’s Immune Development group in Stem Cell medicine at MCRI, who have developed a human “mini-thymus” system, known as a thymus organoid. This laboratory grown organoid faithfully mimics how T cells develop in the human thymus. Using this system, we have shown that unconventional T cells generated in the organoid progress through the same development stages observed in primary human thymus tissue. This confirm that the model accurately reflects human biology.
This mini-thymus system gives us unprecedented ability to directly test what factors are essential for the development of unconventional T cells by selectively removing or altering them. As a result, it is transforming our understanding of how these cells are made in the human body.
Beyond fundamental discovery, this research has exciting therapeutic potential. Unlike conventional T cells, unconventional T cells can be transferred between individuals without causing immune rejection. This makes them ideal candidates for “off-the-shelf” cell therapies. Utilising the thymus organoids, we aim to generate unlimited numbers of unconventional T cells that can be used to treat cancer and infectious diseases.
Together, this research program will deliver new insights into how unconventional T cells are produced in the human body and pave the way towards safe, scalable cellular immunotherapies to improve outcomes for patients with cancer and infection.
Lifespan-immunity research project
Led by Dr Carolien van de Sandt
Our immune system evolves and changes throughout our life to effectively respond to known and unknown threats like viruses. When we are young, our immune system learns to recognize potential threats, and gradually your immunity becomes stronger. However, when we get older, we may become more vulnerable to viral infections and experience reduced effectiveness of vaccines. Our immune system may also respond differently to infections or vaccines when you have an underlying health condition or use certain types of medications, which could potentially increase the risk for severe disease outcomes.
Dr Carolien van de Sandt leads the ambitious Lifespan Immunity project which aims to:
- Define how our immune system develops across the human lifespan and in high-risk populations.
- Understand how underlying conditions affect immune memory formation following infection or vaccination.
The primary outcome of this work is to generate an in-depth understanding of how our immune system functions and changes across the human lifespan and how these functions are affected by underlying conditions or medications. This information will help to improve the identification of high-risk populations, identify potential therapeutic targets and improve treatment and vaccine strategies.
The Lifespan-immunity research project is supported by the National Health and Medical Research Council (NHMRC) investigator Fellowship and the CSL Centenary Fellowship.
Watch the CSL Awards 2026 Centenary Fellowship to Carolien van de Sandt
Funding
- National Health and Medical Research Council (NHMRC)
- The Viertel Charitable Foundation
Collaborations
- Professor Andrew Steer and Dr Joshua Osowicki – Group A Streptococcus
- Professor Fergus Cameron – Type I Diabetes
- Professor Peter Houweling and Dr Chantal Coles – Muscular Dystrophy
- Professor Ed Stanley – Stem Cell Immunotherapies
- Professor Igor Konstantinov – Heart Transplant Rejection
- Professor Stuart Berzins – Unconventional T cell development (Federation University)
Featured publications
More publications available via PubMed.
Taheri M, Menne C, Anderson J, Perriman L, Li S, Berzins SP, Licciardi PV, Ashhurst TM, Jalali S, Pellicci DG. The changing immune landscape of innate-like T cells and other innate cells throughout life. Immunol Cell Biol. 2026 Jan;104(1):74-88. doi: 10.1111/imcb.70070. Epub 2025 Dec 10. PMID: 41376250; PMCID: PMC12800730.
Coles CA, Jalali S, de Valle K, Manton N, Karlaftis V, Attard C, Galea E, Forbes R, Piers AT, Clark DR, Woodcock IR, Pellicci DG, Houweling PJ. Detailed immune cell profiling of paediatric patient with limb girdle muscular dystrophy R3. J Neurol Sci. 2025 Sep 15;476:123629. doi: 10.1016/j.jns.2025.123629. Epub 2025 Jul 18. PMID: 40737975.
Perriman L, Tavakolinia N, Jalali S, Li S, Hickey PF, Amann-Zalcenstein D, Ho WWH, Baldwin TM, Piers AT, Konstantinov IE, Anderson J, Stanley EG, Licciardi PV, Kannourakis G, Naik SH, Koay HF, Mackay LK, Berzins SP, Pellicci DG. A three-stage developmental pathway for human Vγ9Vδ2 T cells within the postnatal thymus. Sci Immunol. 2023 Jul 21;8(85):eabo4365. doi: 10.1126/sciimmunol.abo4365. Epub 2023 Jul 14. PMID: 37450574.
Anderson J, Jalali S, Licciardi PV, Pellicci DG. OMIP-91: A 27-color flow cytometry panel to evaluate the phenotype and function of human conventional and unconventional T-cells. Cytometry A. 2023 Jul;103(7):543-547. doi: 10.1002/cyto.a.24738. Epub 2023 May 14. PMID: 37183268.
Jalali S, Harpur CM, Piers AT, Auladell M, Perriman L, Li S, An K, Anderson J, Berzins SP, Licciardi PV, Ashhurst TM, Konstantinov IE, Pellicci DG. A high- dimensional cytometry atlas of peripheral blood over the human life span. Immunol Cell Biol. 2022 Nov;100(10):805-821. doi: 10.1111/imcb.12594. Epub 2022 Nov 6. PMID: 36218032; PMCID: PMC9828744.
Anderson J, Imran S, Frost HR, Azzopardi KI, Jalali S, Novakovic B, Osowicki J, Steer AC, Licciardi PV, Pellicci DG. Immune signature of acute pharyngitis in a Streptococcus pyogenes human challenge trial. Nat Commun. 2022 Feb 9;13(1):769. doi: 10.1038/s41467-022-28335-3. PMID: 35140232; PMCID: PMC8828729.
Wurzel D, Neeland MR, Anderson J, Abo YN, Do LAH, Donato CM, Bines JE, Toh ZQ, Higgins RA, Jalali S, Cole T, Subbarao K, McMinn A, Dohle K, Haeusler GM, McNab S, Alafaci A, Overmars I, Clifford V, Lee LY, Daley AJ, Buttery J, Bryant PA, Burgner D, Steer A, Tosif S, Konstantinov IE, Duke T, Licciardi PV, Pellicci DG, Crawford NW. A case report describing the immune response of an infant with congenital heart disease and severe COVID-19. Commun Med (Lond). 2021 Nov 15;1:47. doi: 10.1038/s43856-021-00047-7. PMID: 35602234; PMCID: PMC9053208.
Pellicci DG, Koay HF, Berzins SP. Thymic development of unconventional T cells: how NKT cells, MAIT cells and γδ T cells emerge. Nat Rev Immunol. 2020 Dec;20(12):756-770. doi: 10.1038/s41577-020-0345-y. Epub 2020 Jun 24. PMID: 32581346.
Koay HF, Su S, Amann-Zalcenstein D, Daley SR, Comerford I, Miosge L, Whyte CE, Konstantinov IE, d'Udekem Y, Baldwin T, Hickey PF, Berzins SP, Mak JYW, Sontani Y, Roots CM, Sidwell T, Kallies A, Chen Z, Nüssing S, Kedzierska K, Mackay LK, McColl SR, Deenick EK, Fairlie DP, McCluskey J, Goodnow CC, Ritchie ME, Belz GT, Naik SH, Pellicci DG, Godfrey DI. A divergent transcriptional landscape underpins the development and functional branching of MAIT cells. Sci Immunol. 2019 Nov 22;4(41):eaay6039. doi: 10.1126/sciimmunol.aay6039. PMID: 31757835; PMCID: PMC10627559.
Koay HF, Gherardin NA, Enders A, Loh L, Mackay LK, Almeida CF, Russ BE, Nold- Petry CA, Nold MF, Bedoui S, Chen Z, Corbett AJ, Eckle SB, Meehan B, d'Udekem Y, Konstantinov IE, Lappas M, Liu L, Goodnow CC, Fairlie DP, Rossjohn J, Chong MM, Kedzierska K, Berzins SP, Belz GT, McCluskey J, Uldrich AP, Godfrey DI, Pellicci DG. A three-stage intrathymic development pathway for the mucosal-associated invariant T cell lineage. Nat Immunol. 2016 Nov;17(11):1300-1311. doi: 10.1038/ni.3565. Epub 2016 Sep 26. PMID: 27668799.