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CD4 + CD8 +  T lymphocytes account for 1–2% of circulating human T lymphocytes, but their frequency is augmented in several diseases. The phenotypic and functional properties of these T lymphocytes are still ill-defined. We performed an  ex vivo  characterization of CD4 + CD8 +  T lymphocytes from the blood of healthy individuals. We observed that CD4 + CD8 +  T lymphocytes exhibit several characteristics associated with memory T lymphocytes including the expression of chemokine receptors (e.g. CCR7, CXCR3, CCR6) and activation markers (e.g. CD57, CD95). Moreover, we showed that a greater proportion of CD4 + CD8 +  T lymphocytes have an enhanced capacity to produce cytokines (IFNγ, TNFα, IL-2, IL-4, IL-17A) and lytic enzymes (perforin, granzyme B) compared to CD4 +  and/or CD8 +  T lymphocytes. Finally, we assessed the impact of three key cytokines in T cell biology on these cells. We observed that IL-2, IL-7 and IL-15 triggered STAT5 phosphorylation in a greater proportion of CD4 + CD8 +  T lymphocytes compared to CD4 and CD8 counterparts. We demonstrate that CD4 + CD8 +  T lymphocytes from healthy donors exhibit a phenotypic profile associated with memory T lymphocytes, an increased capacity to produce cytokines and lytic enzymes, and a higher proportion of cells responding to key cytokines implicated in T cell survival, homeostasis and activation.

Peripheral human CD4+CD8+ T lymphocytes exhibit a memory phenotype and enhanced responses to IL-2, IL-7 and IL-15