CD5 levels define functionally heterogeneous populations of naïve human CD4+ T cells

• Published in: European journal of immunology Vol. 51; no. 6; pp. 1365 - 1376
• Main Authors: Sood, Aditi, Lebel, Marie‐Ève, Dong, Mengqi, Fournier, Marilaine, Vobecky, Suzanne J., Haddad, Élie, Delisle, Jean‐Sébastien, Mandl, Judith N., Vrisekoop, Nienke, Melichar, Heather J.
• Format: Journal Article
• Language: English
• Published: Germany Wiley Subscription Services, Inc 01-06-2021; John Wiley and Sons Inc
• Subjects: Adaptive immunity; Animal models; Basic; CD4 antigen; CD4+ T cells; CD5; CD5 antigen; Cell culture; Cell surface; Cytokines; Gene expression; Human T cells; Immunological memory; Lymphocytes; Lymphocytes T; Memory cells; Peptides; T cell receptors; Thymus; CD4+ T cells; Cytokines; CD5; Human T cells; Thymus
• ISSN: 0014-2980; 1521-4141
• DOI: 10.1002/eji.202048788

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.
CD5lo and CD5hi naïve human CD4+ T cells differ in their gene expression profiles, affinity for foreign antigen, cytokine production after activation, and accumulation in the memory compartment. These findings have important implications in the identification of functionally biased T‐cell populations that can be exploited to improve cell therapies.