Prof Sarah Rowland-Jones

Research

The theme of our group is anti-viral immunity, with a particular focus on how immune responses modify the outcome of HIV and other viral infections. Our starting point is the question “What determines the outcome of an individual’s encounter with HIV?” – will they resist infection altogether, survive without symptoms for a decade or more or succumb rapidly to immunodeficiency disease? The answer to these questions have important implications for the design of vaccines and immune therapies against HIV infection.

An effective HIV vaccine is desperately needed in developing countries. We work closely with colleagues in Kenya, The Gambia and China to study in detail the immune responses of the local population to local strains of HIV-1 and HIV-2, providing valuable information for vaccine design in these countries.

We address our questions in HIV infection through the study of diverse cohorts (both adults and children born to infected mothers) in several different parts of the world: looking at people with a high degree of HIV exposure who remain persistently seronegative, those acutely infected, and people with chronic infection (progressors or non-progressors) who may be undergoing antiretroviral treatment. A key finding from our group was that some people, particularly sex workers in Kenya and the Gambia, with extensive HIV exposure who remained antibody-negative and apparently uninfected generated cellular immune responses to HIV. In all our cohorts we aim to provide a full characterisation of the cellular immune response to HIV, including CD8+ and CD4+ T cells, antigen presenting cells (dendritic cells) and natural killer (NK) cells, in relation to their clinical status and host genotype, looking also at how their virus evolves under selection pressure from the immune system. We take a similar approach to our studies in cohorts of subjects with dengue virus or avian influenza infection enrolled in the WT Unit in Ho Chi Minh city, Viet Nam (Director, Jeremy Farrar)
The main interest of the group has been the study of CD8+ cytotoxic T lymphocytes (CTLs), which play a major role in the control of many persistent viruses.

Our current work focuses on "CTL quality" and how the particular functional (including T-cell receptor usage) or phenotypic properties of HIV-specific CTL may be involved in effective control of HIV replication. We have studied the interaction of HLA class I molecules with Killer Inhibitory Receptors (KIRs) and have reported that these actions may be specific at the level of KIR and HLA subtypes, together with the bound peptide.

In recent years, the group has collaborated more extensively with the MRC Laboratories in the Gambia, where SR-J is currently Director of Research and heads the Virology programme. Our joint studies have focused on understanding infection with HIV-2, which does not cause disease in the majority of infected people, even though the few subjects that develop AIDS do so in a manner indistinguishable from HIV-1-infected patients. We have several joint PhD/post-doc projects on HIV-2 pathogenesis and immunology between the MRC HIU and the MRC laboratories in the Gambia.

We are also studying T cell responses to the H5N1 avian influenza virus, examining cross reactivity between virus subtypes (human and avian), in both acutely infected and convalescent patients infected with either H5N1 avian influenza virus or and H3N2/H1N1 virus in Viet Nam and UK. We are monitoring the functional changes in T cell memory over time, to study if the quality of the dominant T cell responses has an impact on the clinical outcome of influenza virus infection. These studies will help us to understand the role of T cell immune responses in avian influenza A and give us a better understanding of whether memory T cells contribute to protective immunity or to disease pathogenesis.

We are also interested in Dengue virus specific T cell responses in order to understand the role that they play in the pathogenesis of severe Dengue disease. These studies have shown that high affinity T-cells that are cross-reactive between dengue virus serotypes are elicited in acute infection and secrete higher levels of pro-inflammatory cytokines than serotype-specific cells. We have shown that T regulatory cells play an important role in reducing the symptoms of acute dengue infection.

Key Publications

Feldmann J, Leligdowicz A, Jaye A, Dong T, Whittle H, Rowland-Jones SL. 2009. Downregulation of the T-cell receptor by human immunodeficiency virus type 2 Nef does not protect against disease progression. J Virol, 83 (24), pp. 12968-12972.

Leligdowicz A, Yindom LM, Onyango C, Sarge-Njie R, Alabi A, Cotten M, Vincent T, da Costa C, Aaby P, Jaye A, Dong T, McMichael A, Whittle H, Rowland-Jones S. 2007. Robust Gag-specific T cell responses characterize viremia control in HIV-2 infection. J Clin Invest, 117 (10), pp. 3067-3074.

HIV-2 infection in the majority of infected subjects follows anLühn K, Simmons CP, Moran E, Dung NT, Chau TN, Quyen NT, Thao LETT, Van Ngoc T, Dung NM, Wills B, Farrar J, McMichael AJ, Dong T, Rowland-Jones S. 2007. Increased frequencies of CD4+ CD25(high) regulatory T cells in acute dengue infection. J Exp Med, 204 (5), pp. 979-985. Read abstract | Read more

Thananchai H, Gillespie G, Martin MP, Bashirova A, Yawata N, Yawata M, Easterbrook P, McVicar DW, Maenaka K, Parham P, Carrington M, Dong T, Rowland-Jones S. 2007. Cutting Edge: Allele-specific and peptide-dependent interactions between KIR3DL1 and HLA-A and HLA-B. J Immunol, 178 (1), pp. 33-37.

Duvall MG, Jaye A, Dong T, Brenchley JM, Alabi AS, Jeffries DJ, van der Sande M, Togun TO, McConkey SJ, Douek DC, McMichael AJ, Whittle HC, Koup RA, Rowland-Jones SL. 2006. Maintenance of HIV-specific CD4+ T cell help distinguishes HIV-2 from HIV-1 infection. J Immunol, 176 (11), pp. 6973-6981.