HTLV-1 causes devastating disabling or fatal diseases in about 10% of infected people: either an aggressive T-cell leukaemia known as adult T-cell leukaemia/lymphoma (ATL) or a chronic inflammatory disease of the central nervous system known as HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP), which causes progressive paralysis of the legs.

Aims of the group

• To explain how HTLV-1 persists in vivo despite the strong host immune response.
• To explain why 10% of individuals develop these serious diseases whereas most remain asymptomatic, and;
• To identify new approaches to treat the malignant and inflammatory diseases.

We use a broad range of approaches, including molecular and cellular immunology, molecular virology, cell biology and mathematical biology. The group has made several contributions whose significance goes beyond HTLV-1 infection, including:

• discovery of tissue-resident antigen-specific T lymphocytes (J Exp Med 1998)
• discovery of T-cell fratricide (Immunity 2000)
• discovery of preferential infection of HTLV-1-specific T cells (Immunity 2000)
• discovery of the virological synapse (Science 2003)
• protective role of single HLA class 1 genes in viral infection at the population level (PNAS 1999)
• the importance of CD8+ T-cell quality in protection against persistent viruses (Science 1996)
• regulation of HTLV-1 clonality and latency in vivo (Blood, PLoS Pathogens, PNAS etc, 2011-2016).

Dr Becca Asquith leads the mathematical biology group, which is internationally recognised for its contributions to the understanding of the dynamics of the immune response, especially in persistent infections such as HIV-1, HTLV-1 and hepatitis C virus.

We study host-pathogen dynamics, with a focus on the interaction between the human CD8+ T cell response and persistent viral infections such as HIV-1, HCV and HTLV-1. We are particularly interested in the impact on clinical outcome and human health of quantitative changes in the key parameters of this dynamic interaction (e.g. CD8+ T cell lysis rate, pathogen replication rate.

Many questions in basic human immunology are difficult to address with traditional techniques. The experimental developments which have revolutionised murine immunology are often not suitable for use in humans. We are therefore developing an alternative approach that combines theoretical techniques with minimally invasive human studies. We use a range of theoretical techniques including deterministic and stochastic mechanistic modelling, bioinformatics, machine learning, Bayesian and frequentist statistics and empirical approaches.

Recent contributions include:

• A reevaluation of the lifespan of human neutrophils in vivo. This work successfully challenged a recent landmark paper claiming blood neutrophils had a long lifespan of >5 days.
• Work on the role of killer immunoglobulin-like receptors (KIRs). This family of receptors are known for their importance in modulating the innate NK cell-mediated response. We have shown that KIRs also modulate the adaptive CD8+ T cell-mediated response with direct consequences for human health. The mechanism and scope of this effect is an area we are actively researching.
• Development of tools to quantify lymphocyte dynamics in humans in vivo. Current applications include quantification of the impact of BCR-antagonists in the treatment of chronic lymphocytic leukaemia, investigation of the dynamics of human stem cell-like memory T cells and the rate of development of “senescent” CD57+ CD8+ T cells.
• Investigation of the relative contribution of lytic and non-lytic CD8+ T cell effectors in the control of infection in SIV-infected rhesus macaques. 
• Quantification of the rate of CD8+ T cell lysis of cells productively infected with HIV-1 in humans in vivo.

Dr Keith Gould has a long-standing research interest in the major histocompatibility complex and its role in antiviral immunity. In addition to research activities, Dr Gould plays a significant role in teaching. He is Leader for the Theme "Molecules, Cells and Disease" in years 1 and 2 of Undergraduate Medicine, and is Deputy Head of years 1 and 2 in Undergraduate Medicine. Dr Gould was given an Imperial College Award for Excellence in Teaching in both 2002 and 2007.

Dr Pascale Kropf’s group investigates the immune response to the protozoan parasite leishmania, with extensive involvement in both field work and teaching activities in Ethiopia.