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Studies in murine models show that subthreshold TCR interactions with self-peptide are required for thymic development and peripheral survival of naïve T cells. Recently, differences in the strength of tonic TCR interactions with self-peptide, as read-out by cell surface levels of CD5, were associated with distinct effector potentials among sorted populations of T cells in mice. However, whether CD5 can also be used to parse functional heterogeneity among human T cells is less clear. Our study demonstrates that CD5 levels correlate with TCR signal strength in human naïve CD4+ T cells. Further, we describe a relationship between CD5 levels on naïve human CD4+ T cells and binding affinity to foreign peptide, in addition to a predominance of CD5hi T cells in the memory compartment. Differences in gene expression and biases in cytokine production potential between CD5lo and CD5hi naïve human CD4+ T cells are consistent with observations in mice. Together, these data validate the use of CD5 surface levels as a marker of heterogeneity among human naïve CD4+ T cells with important implications for the identification of functionally biased T- cell populations that can be exploited to improve the efficacy of adoptive cell therapies. © 2021 The Authors. European Journal of Immunology published by Wiley-VCH GmbH.

Citation

Aditi Sood, Marie-Ève Lebel, Mengqi Dong, Marilaine Fournier, Suzanne J Vobecky, Élie Haddad, Jean-Sébastien Delisle, Judith N Mandl, Nienke Vrisekoop, Heather J Melichar. CD5 levels define functionally heterogeneous populations of naïve human CD4+ T cells. European journal of immunology. 2021 Jun;51(6):1365-1376

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PMID: 33682083

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