Affiliation:
1. School of Infection and Immunity University of Glasgow Glasgow UK
2. Baker Heart and Diabetes Institute & Baker Department of Cardiometabolic Health University of Melbourne Melbourne Australia
3. Malawi Liverpool Wellcome Centre Blantyre Malawi
4. School of Cancer Sciences University of Glasgow Glasgow UK
5. Department of Pathology and Immunology Washington University St Louis Missouri USA
Abstract
AbstractCytokine production by memory T cells is a key mechanism of T cell mediated protection. However, we have limited understanding of the persistence of cytokine producing T cells during memory cell maintenance and secondary responses. We interrogated antigen‐specific CD4 T cells using a mouse influenza A virus infection model. Although CD4 T cells detected using MHCII tetramers declined in lymphoid and non‐lymphoid organs, we found similar numbers of cytokine+ CD4 T cells at days 9 and 30 in the lymphoid organs. CD4 T cells with the capacity to produce cytokines expressed higher levels of pro‐survival molecules, CD127 and Bcl2, than non‐cytokine+ cells. Transcriptomic analysis revealed a heterogeneous population of memory CD4 T cells with three clusters of cytokine+ cells. These clusters match flow cytometry data and reveal an enhanced survival signature in cells capable of producing multiple cytokines. Following re‐infection, multifunctional T cells expressed low levels of the proliferation marker, Ki67, whereas cells that only produce the anti‐viral cytokine, interferon‐γ, were more likely to be Ki67+. Despite this, multifunctional memory T cells formed a substantial fraction of the secondary memory pool. Together these data indicate that survival rather than proliferation may dictate which populations persist within the memory pool.
Subject
Immunology,Immunology and Allergy
Cited by
1 articles.
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