Functional heterogeneity of human memory CD4+ T cell clones primed by pathogens or vaccines

S Becattini, D Latorre, F Mele, M Foglierini… - Science, 2015 - science.org
S Becattini, D Latorre, F Mele, M Foglierini, C De Gregorio, A Cassotta, B Fernandez…
Science, 2015science.org
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 …
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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