Functional and phenotypic characterization of tetanus toxoid-specific human CD4+ T cells following re-immunization.
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-7Ralpha) 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-7Ralpha 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-7Ralpha(high)Bcl-2(high) 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-gamma, down-regulated CCR7, IL-7Ralpha 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-7Ralpha(high)Bcl-2(high) 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-7Ralpha expression levels might be a useful marker for identifying long-lived Ag-specific CD4(+ )T cells in memory T cells.
Cellerai
Cristina
C
Laboratory of AIDS Immunopathogenesis, Division of Immunology and Allergy, Department of Medicine, Centre Hospitalier Universitaire Vaudois, University of Lausanne, Lausanne, Switzerland.
Harari
Alexandre
A
Vallelian
Florence
F
Boyman
Onur
O
Pantaleo
Giuseppe
G
D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism; D018984:Epitopes, T-Lymphocyte / Q000008:administration & dosage / Q000276:immunology*; D006801:Humans; D007117:Immunization, Secondary; D007156:Immunologic Memory; D016130:Immunophenotyping; D013745:Tetanus Toxoid / Q000008:administration & dosage / Q000276:immunology*
D016207:Cytokines; D018984:Epitopes, T-Lymphocyte; D013745:Tetanus Toxoid