Immune regulation in respiratory virus infections

Lead Research Organisation: MRC National Inst for Medical Research

Abstract

The immune response to infection is regulated, both qualitatively and quantitatively by the CD4 T-lymphocyte, by their release of hormone-like substances or lymphokines, interferons or interleukins (IL-4, 5, 10) on encounter with pathogen or vaccine. We hope to understand at the molecular level the mechanisms that determine which type of interferon or lymphokine is produced by virus-specific T-lymphocytes on encounter with pathogen.

Technical Summary

1. General Aims Relevance Health Issues. There are distinct differences in the type of immune response, both effectiveness and longevity (memory) induced by natural infection (long-lived, effective) or vaccination (short-lived, partial). An understanding of the unique features of immune memory, recruited by infection, might offer some considerable potential for improving the immune status to vaccines by recombinant DNA technology. 2. Precise Scientific Objectives. To understand the molecular mechanism(s) that regulate(s) T-lymphocyte development during virus infection, by clonal (single cell) analysis of the immune memory population. T cell clones are characterised for virus recognition specificity and lymphokine secretion profile. Difference analysis of cDNA products from sibling clones, which produce different lymphokines (Th1 for interferon-g or Th2 for IL-4, IL-5) to determine the regulatory elements of T cell development in infection. 3. Plan of Investigation. A library of T-lymphocyte clones have been established from individual inbred mice, following viral infection, whose recognition specificity, receptor gene usage and lymphokine profile have been well characterised. We are employing a subtractive cDNA approach to identify novel transcription factors that may be implicated in lymphokine gene regulation. Representational Difference Analysis is being performed on matched pairs of sibling T cell clones, following receptor ligation by antigen and activation. Difference (cDNA) products are being characterised at defined time points. 4 . Subsequent Scientific/Medical Opportunities. The profile of lymphokines produced following viral infection or vaccination are crucial to effective immunity. Knowledge of their regulation, at the molecular level, may be of direct relevance to our understanding of disease susceptibility and vaccine efficacy.

Publications

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