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CD8(+) T cells can exert both protective and harmful effects on the virus-infected host. However, there is no systematic method to identify the attributes of a protective CD8(+) T cell response. Here, we combine theory and experiment to identify and quantify the contribution of all HLA class I alleles to host protection against infection with a given(More)
Human T-lymphotropic virus type 1 (HTLV-1) is a persistent CD4+ T-lymphotropic retrovirus. Most HTLV-1-infected individuals remain asymptomatic, but a proportion develop adult T cell leukemia or inflammatory disease. It is not fully understood how HTLV-1 persists despite a strong immune response or what determines the risk of HTLV-1-associated diseases.(More)
Understanding the role of cytotoxic T lymphocytes (CTLs) in controlling HIV-1 infection is vital for vaccine design. However, it is difficult to assess the importance of CTLs in natural infection. Different human leukocyte antigen (HLA) class I alleles are associated with different rates of progression to AIDS, indicating that CTLs play a protective role.(More)
Infection and gene expression by the human T lymphotropic virus type I (HTLV-I) in vivo have been thought to be confined to CD4(+) T lymphocytes. We show here that, in natural HTLV-I infection, a significant proportion of CD8(+) T lymphocytes are infected by HTLV-I. Interestingly, HTLV-I-specific but not Epstein-Barr virus-specific CD8(+) T lymphocytes were(More)
Information about the kinetic behavior and lifespan of lymphocytes is crucial to understanding the mechanisms that regulate processes such as immunologic memory. We have used in vivo labeling of dividing cells with 6,6-(2)H(2)-glucose, combined with cell sorting and gas-chromatography-mass spectrometry for deuterium enrichment, in order to analyze the(More)
Human T-lymphotropic virus type 1 (HTLV-1) is a pathogenic retrovirus that infects human CD4(+) T lymphocytes. Despite its presence in T cells, HTLV-1 causes little overt immunosuppression. This host-virus relationship has therefore been exploited as an excellent model system for studying the dynamic interaction between a persistent retrovirus and the(More)
Human natural killer (NK) cells form a circulating population in a state of dynamic homeostasis. We investigated NK cell homeostasis by labelling dividing cells in vivo using deuterium-enriched glucose in young and elderly healthy subjects and patients with viral infection. Following a 24-hr intravenous infusion of 6,6-D(2)-glucose, CD3(-) CD16(+) NK cells(More)
Mathematics is a useful tool in the analysis and understanding of population dynamic aspects of the immune response. However, the power of mathematical modelling in immunology is frequently limited by the shortage of experimental data. Here, we review the contribution of mathematics to two areas of immunology. We highlight the problem caused by lack of(More)
Quantitative knowledge of the turnover of different leukocyte populations is a key to our understanding of immune function in health and disease. Much progress has been made thanks to the introduction of stable isotope labeling, the state-of-the-art technique for in vivo quantification of cellular life spans. Yet, even leukocyte life span estimates on the(More)
Cell proliferation may be measured in vivo by quantifying DNA synthesis with isotopically labeled deoxyribonucleotide precursors. Deuterium-labeled glucose is one such precursor which, because it achieves high levels of enrichment for a short period, is well suited to the study of rapidly dividing cells, in contrast to the longer term labeling achieved with(More)