Functional and phenotypic characterization of tetanus toxoid-specific human CD4± T cells following re-immunization

Abstract

The formation of immunological memory is a hallmark of adaptive immunity and the goal of vaccination. For CD8+ T cells, successful generation of memory cells has been linked to IL-7 receptor alpha (IL-7Rα) expression, suggesting a role for IL-7 signaling, which in turn is important for preventing T cell apoptosis. We thus investigated the kinetics and changes of IL-7Rα, and anti-apoptotic protein Bcl-2 expression levels in tetanus toxoid (TT)-specific CD4+ T cells at different time points prior and after TT re-immunization of TT-immune individuals. Prior to re-immunization, most TT-specific CD4+ T cells were high IL-2 producers, CD45RA-CCR7+, IL-7Rα high Bcl-2high cells, resembling typical long-lived central memory cells. Already 5 days, and more importantly at the peak of the response, after TT re-immunization, a substantial fraction of these cells secreted also IFN-γ, down-regulated CCR7, IL-7Rα and Bcl-2 and became Ki67 positive, resembling effector memory cells. In contrast, TT-specific CD4+ T cells found 60 days or later after re-immunization were again as baseline. Interestingly, a significant fraction of IL-7Rαhigh Bcl-2high TT-specific CD4+ T cells, i.e. the proposed memory cell precursors, remained stable at any time point upon re-immunization. Together, these results suggest that IL-7Rα expression levels might be a useful marker for identifying long-lived Ag-specific CD4+ T cells in memory T cells. © 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.