Award details

Memory Group

Reference	BBS/E/E/0000ME00
Principal Investigator / Supervisor	Dr David Tough
Co-Investigators / Co-Supervisors
Institution	Edward Jenner Institute for Vaccine Res
Department	Scientific Head
Funding type	Research
Value (£)	711,000
Status	Completed
Type	Institute Project
Start date	01/04/1997
End date	31/10/2005
Duration	103 months

Abstract

Aim - to investigate the characteristics of the cells mediating immune memory and the factors that regulate their generation and long term survival. During a typical immune response to infection, antigen-specific lymphocytes divide extensively, generating a high number of effector cells. Once the infectious agent has been cleared, these effector cells are no longer needed and the vast majority of them die by apoptosis. However, some the activated cells survive long- term and carry immunological memory to the original priming antigen; memory reflects an increased frequency of antigen- specific T and B cells, an increased sensitivity of these cells to antigenic activation and the persistence of direct effector functions. The mechanisms underlying the generation and maintenance of the memory cells remain largely unknown. Since memory is not the inevitable outcome of antigenic challenge, and experimental immunisation may induce only short-lived responses or even tolerance, information about these issues is of key importance for the rational design of vaccines. Adjuvant Activity of Microbial Components and Cytokines:- The addition of adjuvants to vaccine formulations allows for the generation of strong immune responses and the production of immune memory against substances with low inherent immunogenicity. Possible mechanisms of adjuvant action include influencing the ability of antigen presenting cells to present antigen and/or modulating the competency of lymphocytes to be activated upon antigen encounter. We are investigating how components of microorganisms, and the cytokines they induce affect the initial priming of T cells and the generation of long-lived memory cells. Properties of Memory T Cells:- At present, there are no markers that conclusively identify memory T cells, distinguishing them from naive cells and recently activated effectors. For this reason, memory T cells have remained a poorly defined population. We are studying the properties of memory T cells, focussing on determining their state of activation and kinetic behaviour in animal models and in humans. In addition, we are seeking definitive genetic markers for memory T cells. Lymphocyte Homeostasis:- The observations that lymphocytes are maintained at relatively constant numbers under 'resting' conditions, and that T and B cell numbers return to these resting levels after the resolution of acute immune responses have been cited as evidence that lymphocytes are under homeostatic control. Homeostasis is presumed to reflect a limit in the number of lymphocytes that can be sustained by available survival factors. Nevertheless, direct evidence for homeostatic control of lymphocytes is sparse, and the nature of the putative survival factors is unknown. We are examining the potential impact of homeostatic mechanisms on the long-term maintenance of immune memory, with a particular interest in the role of cytokines. Generation of T Cell Memory:- The vast majority (greater than 95 per cent) of T cells activated during an acute immune response die, with the remainder surviving long- term and carrying immunological memory. Remarkably, very little is known about the factors that allow for the establishment of the memory T cell pool. We are investigating several different parameters that might affect the generation of memory T cells, including the affinity of TCR for antigen, the type of antigen-presenting cell on which T cells encounter antigen and the microenvironment in which T cells are activated.

Summary

unavailable

Committee	Closed Committee - Animal Sciences (AS)
Research Topics	X – not assigned to a current Research Topic
Research Priority	X – Research Priority information not available
Research Initiative	X - not in an Initiative
Funding Scheme	X – not Funded via a specific Funding Scheme

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