Selected publications

• Kok W L, Denney L, Benam K, Cole S, Clelland C, McMichael A J, and Ho L P (2011) Pivotal Advance: Invariant NKT cells reduce accumulation of inflammatory monocytes in the lungs and decrease immune-pathology during severe influenza A virus infection. J Leukoc Biol.

• Benam Kambez H, Kok Wai L, McMichael Andrew J, and Ho Ling-Pei (2011) Alternative spliced CD1d transcripts in human bronchial epithelial cells. PLoS One, 6(8):e22726.

• Denney Laura, Aitken Celia, Li Chris K, Wilson-Davies Eleri, Kok Wai L, Clelland Colin, Rooney Kevin, Young Duncan, Dong Tao, McMichael Andrew J, Carman William F, and Ho Ling-Pei (2010) Reduction of natural killer but not effector CD8 T lymphocytes in three consecutive cases of severe/lethal H1N1/09 influenza A virus infection. PLoS One, 5(5):e10675.

• Lockstone Helen E, Sanderson Sharon, Kulakova Nina, Baban Dilair, Leonard Andrew, Kok Wai L, McGowan Simon, McMichael Andrew J, and Ho Ling-Pei (2010) Gene set analysis of lung samples provides insight into pathogenesis of progressive, fibrotic pulmonary sarcoidosis. Am J Respir Crit Care Med, 181(12):1367-75.

• Ho Ling-Pei, Denney Laura, Luhn Kerstin, Teoh Denise, Clelland Colin, and McMichael Andrew J (2008) Activation of invariant NKT cells enhances the innate immune response and improves the disease course in influenza A virus infection. Eur J Immunol, 38(7):1913-22.

Ling-Pei Ho

The overall aim of our work is to better understand the regulation of immune responses in the lungs. We are particularly interested in the role of invariant natural killer T (iNKT) cells in this process, and the mechanisms with which they direct outcome in T cell-mediated immune diseases. iNKT cells are a unique subset of T cells with immune-regulatory properties. They recognise self and microbial glycolipid antigens in the context of the MHC class I-related glycoprotein, CD1d, and when stimulated, have a wide-ranging effect on other immune cells. In mice, iNKT can reduce tumour metastases, enhance immune response to pathogens, and halt progression of T cell mediated autoimmune diseases like type I diabetes mellitus and multiple sclerosis. iNKT cells are deficient in many human diseases characterised by chronic and/or disseminated T cell activation e.g. sarcoidosis, inflammatory bowel disease, Wegener’s granulomatosis and HIV AIDS. We were among the first to report this deficiency  (in sarcoidosis) and since then our work has branched into these areas:

Molecular regulation of CD1d gene expression in the lungs. This project investigates the factors and stimuli involved in molecular regulation of CD1d gene expression in human lung epithelial cells and how this contributes to mucosal immune defence.     

Role of iNKT cells in modulation of lung immunepathology in influenza A virus infection. We have shown that iNKT cell activation improves outcome of influenza A virus infection in murine models and that deficiency of these cells causes significant increase in mortality. We are now dissecting the mechanisms of iNKT-related immune-protection in this infection and how iNKT cells interact with other immune and inflammatory cells in the lungs. We are also collaborating with John Skehel and John McCauley at the National Institute of Medical Research, Mill Hill to study these effects in H5N1 virus infection.

Functional and kinetic analysis of iNKT cell subsets in vivo and how they affect disease genesis. Having demonstrated that human iNKT cells comprise different functional subsets, we now focus on understanding how these subsets influence immune responses in vivo. For this we use a model of T cell-mediated immune disease (experimental autoimmune encephalitis) to track the phenotypic and functional changes of these iNKT subsets and how they influence disease-causing T cells.

. Sarcoidosis is the archetypal disease of immune dysregulation. In these patients, T cells and macrophages are hyper-activated resulting in granulomatous deposits, mainly in the lungs, though all organs can be affected. The cause of this disease is unknown. We are interested in the aetio-pathogenesis of this disease and in translating this understanding to improvement in clinical treatment. Current studies include micro-array gene profiling of lung biopsies and T cells derived from lung lavage from patients to identify global disturbances in expression of immune genes. This work forms the basic research arm of the Oxford Sarcoidosis Clinic at the Oxford Centre for Respiratory Medicine.