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Publication : Stimulation by soluble CD70 promotes strong primary and secondary CD8+ cytotoxic T cell responses in vivo.

First Author  Rowley TF Year  2004
Journal  J Immunol Volume  172
Issue  10 Pages  6039-46
PubMed ID  15128787 Mgi Jnum  J:89859
Mgi Id  MGI:3041755 Doi  10.4049/jimmunol.172.10.6039
Citation  Rowley TF, et al. (2004) Stimulation by soluble CD70 promotes strong primary and secondary CD8+ cytotoxic T cell responses in vivo. J Immunol 172(10):6039-46
abstractText  Identification of the signals required for optimal differentiation of naive CD8(+) T cells into effector and memory cells is critical for the design of effective vaccines. In this study we demonstrate that CD27 stimulation by soluble CD70 considerably enhances the magnitude and quality of the CD8(+) T cell response. Stimulation with soluble CD70 in the presence of Ag significantly enhanced the proliferation of CD8(+) T cells and their ability to produce IL-2 and IFN-gamma in vitro. Administration of Ag and soluble CD70 resulted in a massive (>300-fold) expansion of Ag-specific CD8(+) T cells in vivo, which was due to the enhanced proliferation and survival of activated T cells. In mice that received Ag and soluble CD70, CD8(+) T cells developed into effectors with direct ex vivo cytotoxicity. Furthermore, unlike peptide immunization, which resulted in a diminished response after rechallenge, CD27 stimulation during the primary challenge evoked a strong secondary response upon rechallenge with the antigenic peptide. Thus, in addition to increasing the frequency of primed Ag-specific T cells, CD27 signaling during the primary response instills a program of differentiation that allows CD8(+) T cells to overcome a state of unresponsiveness. Taken together these results demonstrate that soluble CD70 has potent in vivo adjuvant effects for CD8(+) T cell responses.
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