Human Naive T Cells Express Functional CXCL8 and Promote Tumorigenesis

Naive T cells are thought to be functionally quiescent. In this study, we studied and compared the phenotype, cytokine profile, and potential function of human naive CD4⁺ T cells in umbilical cord and peripheral blood. We found that naive CD4⁺ T cells, but not memory T cells, expressed high levels of chemokine CXCL8. CXCL8⁺ naive T cells were preferentially enriched CD31⁺ T cells and did not express T cell activation markers or typical Th effector cytokines, including IFN-γ, IL-4, IL-17, and IL-22. In addition, upon activation, naive T cells retained high levels of CXCL8 expression. Furthermore, we showed that naive T cell-derived CXCL8 mediated neutrophil migration in the in vitro migration assay, supported tumor sphere formation, and promoted tumor growth in an in vivo human xenograft model. Thus, human naive T cells are phenotypically and functionally heterogeneous and can carry out active functions in immune responses.