Research Article

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

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Science  04 Dec 2014:
1260668
DOI: 10.1126/science.1260668

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Abstract

Distinct types of CD4+ T cells protect the host against different classes of pathogens. However, whether a given pathogen induces a single type of polarized T cell is unclear. By combining antigenic stimulation and T cell receptor deep sequencing we show 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 priming.

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