CD5 levels define functionally heterogeneous populations of naïve human CD4+ T cells. Issue 6 (19th March 2021)

• Record Type: Journal Article
• 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.
• Is Part Of: European journal of immunology. Volume 51:Issue 6(2021)
• Page Start: 1365
• Page End: 1376
• Publication Date: 2021-03-19
• Subjects: Cytokines -- CD4+ T cells -- CD5 -- Human T cells -- Thymus; Immunology -- Periodicals; 616.079
• DOI: 10.1002/eji.202048788
• Languages: English
• ISSNs: 0014-2980

Abstract

Abstract: 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 CD5 hi T cells in the memory compartment. Differences in gene expression and biases in cytokine production potential between CD5 lo and CD5 hi 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. Abstract : CD5 lo and CD5 hi 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.