Functional heterogeneity of human memory CD4+ T cell clones primed by pathogens or vaccines
For T cells, variety is the spice of life
CD4+ helper T cells come in a variety of flavors. This allows them to respond in a manner that is tailored to the pathogen they encounter. Becattini et al. wondered whether multiple “flavors” of human CD4+ T cells respond to specific stimuli or if just one flavor dominates. To find out, they stimulated human memory CD4+ T cells with a fungus, a bacteria, or a vaccine antigen. Multiple helper cell subsets participated in each response. T cell receptor sequencing revealed that in some cases, T cells with the same specificity acquired different helper cell fates. Thus, there is more heterogeneity in human T cell responses than previously appreciated.
Science, this issue p. 400
Abstract
Distinct types of CD4+ T cells protect the host against different classes of pathogens. However, it is unclear whether a given pathogen induces a single type of polarized T cell. By combining antigenic stimulation and T cell receptor deep sequencing, we found that human pathogen- and vaccine-specific T helper 1 (TH1), TH2, and TH17 memory cells have different frequencies but comparable diversity and comprise not only clones polarized toward a single fate, but also clones whose progeny have acquired multiple fates. Single naïve T cells primed by a pathogen in vitro could also give rise to multiple fates. Our results unravel an unexpected degree of interclonal and intraclonal functional heterogeneity of the human T cell response and suggest that polarized responses result from preferential expansion rather than priming.
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Supplementary Material
Summary
Materials and Methods
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Tables S1 and S2
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Science
Volume 347 | Issue 6220
23 January 2015
23 January 2015
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Copyright © 2015, American Association for the Advancement of Science.
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Received: 1 September 2014
Accepted: 25 November 2014
Published in print: 23 January 2015
Acknowledgments
We thank D. Jarrossay for cell sorting; O. Petrini, C. Fragoso, and A. Sette for providing valuable reagents; the Adaptive Biotechnologies team for technical support; and S. Monticelli for critical reading of the manuscript. The data presented in this manuscript are tabulated in the main paper and in the supplementary materials. All TCR sequences are available in the supplementary materials as .txt files. FASTA format files are available at downloads.adaptivebiotech.com (username: SallustoSciDec2014data; password: di2PhaiT). The sequences have been deposited in the Gene Expression Omnibus (accession numbers xxxxxx). Supported by European Research Council grant 323183 PREDICT (F.S.), Swiss National Science Foundation grants 149475 (F.S.) and 147662 (A.L.), and European Commission grants FP7-HEALTH-2011-280873, ADITEC (A.L. and F.S.) and FP7-HEALTH-2013-601958, SUPERSIST (T.N.S.). The Institute for Research in Biomedicine is supported by the Helmut Horten Foundation.
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