题名：IL-12 controls cytotoxicity of a novel subset of self-antigen-specific human CD28+ cytolytic T cells.
作者：Barbey C, Baumgaertner P, Devevre E, Rubio-Godoy V, Derre L, Bricard G, Guillaume P, Luescher IF, Lienard D, Cerottini JC, Romero P, Rufer N, Speiser DE. Related Articles, Links
来源：J Immunol[IF=6.387]. 2007 Mar 15;178(6):3566-74.
摘要： Catherine Barbey2,*, Petra Baumgaertner2,*, Estelle Devevre*, Verena Rubio-Godoy*, Laurent Derre*, Gabriel Bricard*, Philippe Guillaume, Immanuel F. Luescher, Danielle Linard*, Jean-Charles Cerottini*,, Pedro Romero*,, Nathalie Rufer2,, and Daniel E. Speiser2,3,*,
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1 This study was sponsored and supported by the Ludwig Institute for Cancer Research, the Cancer Research Institute (New York), the Swiss Cancer League/Oncosuisse Grant 01323-02-2003, the Emma Muschamp Foundation, the Swiss National Science Foundation Grant 3200B0-107693, and the Swiss National Center of Competence in Research Molecular Oncology.
2 C.B., P.B., N.R., and D.E.S. contributed equally to this work.
3 Address correspondence and reprint requests to Dr. Daniel E. Speiser, Division of Clinical Onco-Immunology, Ludwig Institute for Cancer Research, H?pital Orthopdique, Niveau 5 Est, Avenue Pierre-Decker 4, CH-1005 Lausanne, Switzerland. E-mail address: firstname.lastname@example.org
4 Abbreviations used in this paper: EM, effector memory; DC, dendritic cell; Melan-A, melanoma Ag-A.
* Division of Clinical Onco-Immunology, Ludwig Institute for Cancer Research, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland; Ludwig Institute for Cancer Research, Lausanne Branch, University of Lausanne, Epalinges, Switzerland; Swiss Institute for Experimental Cancer Research, Epalinges, Switzerland; and National Center for Competence in Research, Molecular Oncology, Epalinges, Switzerland
Activated CD8 T cells develop cytotoxicity against autologous cells bearing foreign Ags and self/tumor Ags. However, self-specific cytolysis needs to be kept under control to avoid overwhelming immunopathology. After peptide vaccination of melanoma patients, we studied molecular and functional properties of T cell subsets specific for the self/tumor Ag Melan-A/MART-1. Ex vivo analysis revealed three Ag-specific effector memory (EM) populations, as follows: CD28-negative EM (EM28C) T cells strongly expressing granzyme/perforin, and two EM28+ subsets, one with high and the other with low level expression of these cytotoxic proteins. For further functional characterization, we generated 117 stable CD8 T cell clones by ex vivo flow cytometry-based sorting of these subsets. All EM28C-derived clones lysed target cells with high efficacy. In contrast, EM28+-derived clones were heterogenous, and could be classified in two groups, one with high and the other with low killing capacity, correlating with granzyme/perforin expression. High and low killer phenotypes remained surprisingly stable for several months. However, strongly increased granzyme expression and cytotoxicity were observed after exposure to IL-12. Thus, the data reveal a newly identified subset of CD28+ conditional killer T cells. Because CD28 can mediate strong costimulatory signals, tight cytotoxicity control, as shown in this study through IL-12, may be particularly important for subsets of T cells expressing CD28. 8: