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Heterospecific CD4 Help to Rescue CD8 T Cell Killers¹

Marie-Ghislaine de Goër de Herve^2,*, Anne Cariou^2,*, Federico Simonetta^* and Yassine Taoufik^3,*,,

^* Institut National de la Santé et de la Recherche Médicale, Unite d’Immunologie Biologique, Hôpital de Bicêtre, and Faculté de Médecine, Université Paris 11, Le Kremlin-Bicêtre, France

Help from CD4 T cells may be required for optimal generation and maintenance of memory CD8 T cells and also for optimal Ag reactivation. We examined whether the helper cell and the CD8 killer cell need to have the same Ag specificity for help to be effective during interactions of memory T cells with mature APC. This is important because virus and tumor Ag-specific CD4 T cell responses are selectively impaired in several chronic viral infections and malignancies. We performed studies in vitro and in vivo and found that functional memory CD4 T cells generated from a distinct antigenic source (heterospecific helpers) could provide direct and effective help to memory CD8 T cells. Functional heterospecific memory CD4 T cells could also rescue secondary CD8 T cell responses in an experimental tumor model in which homospecific CD4 help was impaired. This could provide a rationale for immunotherapy strategies designed to bypass impaired homospecific help.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ This work was supported by grants from Association pour la Recherche contre le Cancer and Académie Nationale de Médecine.

² M.-G.G.H. and A.C. contributed equally to the work.

³ Address correspondence and reprint requests to Dr. Y. Taoufik, Institut National de la Santé et de la Recherche Médicale U-802, Faculté de Médecine Paris 11, 63 Rue Gabriel Péri, 94276 Le Kremlin-Bicêtre. E-mail address: yassine.taoufik{at}u-psud.fr

⁴ Abbreviations used in this paper: DC, dendritic cell; LLC, Lewis lung carcinoma; BMDC, bone marrow-derived DC; TIL, tumor-infiltrating lymphocyte; TRAIL, TNF-related apoptosis-inducing ligand.