The relationship between human effector and memory T cells measured by ex vivo and cultured ELISPOT following recent and distal priming

Todryk, Stephen, Pathan, Ansar, Keating, Sheila, Porter, David, Berthoud, Tamara, Thompson, Fiona, Klenerman, Paul and Hill, Adrian (2009) The relationship between human effector and memory T cells measured by ex vivo and cultured ELISPOT following recent and distal priming. Immunology, 128 (1). pp. 83-91. ISSN 0019-2805

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Official URL: http://dx.doi.org/10.1111/j.1365-2567.2009.03073.x

Abstract

Maintenance of T-cell responses is an essential feature in protection from many infectious diseases that must be harnessed in vaccination. The relationship between effector T-cell responses and more durable and highly proliferative T-cell memory, particularly in humans, is not well understood. In this study, effector T-cell responses were measured by overnight ex vivo interferon-γ (IFN-γ) enzyme-linked immunosorbent spot-forming cell assay (ELISPOT), whereas memory T cells were measured by 10-day culture followed by IFN-γ ELISPOT (cultured ELISPOT). We observed a significant correlation between IFN-γ responses to CD4-stimulatory, but not to CD8-stimulatory, recall antigens measured by these assays, suggesting a divergence in regulation. In vaccine trial participants who received a prime-boost vaccination regimen comprising malaria antigens delivered by poxviruses, there was a correlation between ex vivo and cultured responses on day 7, but not 3 months post-vaccination, with the ratio of cultured : ex vivo response increasing over time. To compare responses revealed by cultured ELISPOT in more detail, tetramers comprising viral recall antigens were used to ascribe effector-memory and central-memory T-cell phenotypes through CCR7 and CD62L costaining. For CD8+ responses the effector phenotype decreased during the initial culture period and memory populations remained high within the resulting 20-fold to 50-fold increased IFN-γ-secreting or tetramer+ population. This was less marked for CD4+ responses, which had higher starting memory phenotype. Depletion of these central-memory T-cell populations generally ablated responses in cultured ELISPOT and reduced ex vivo responses. This study highlights differences between CD4+ and CD8+ effector and memory T cells, and the more complex phenotype of CD4+ T cells.

Item Type: Article
Subjects: B900 Others in Subjects allied to Medicine
C100 Biology
C700 Molecular Biology, Biophysics and Biochemistry
Department: Faculties > Health and Life Sciences > School of Life Sciences > Applied Sciences
Depositing User: EPrints Services
Date Deposited: 19 Apr 2010 09:07
Last Modified: 01 Mar 2016 16:12
URI: http://nrl.northumbria.ac.uk/id/eprint/3023

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