AUTHOR=Muraro Elena, Merlo Anna, Martorelli Debora, Cangemi Michela, Dalla Santa Silvia, Dolcetti Riccardo, Rosato Antonio TITLE=Fighting Viral Infections and Virus-Driven Tumors with Cytotoxic CD4+ T Cells JOURNAL=Frontiers in Immunology VOLUME=8 YEAR=2017 URL=https://www.frontiersin.org/articles/10.3389/fimmu.2017.00197 DOI=10.3389/fimmu.2017.00197 ISSN=1664-3224 ABSTRACT=CD4+ T cells have been and are still largely regarded as the orchestrators of immune responses, being able to differentiate into distinct T helper cell populations based on differentiation signals, transcription factor expression, cytokine secretion, and specific functions. Nonetheless, a growing body of evidence indicates that CD4+ T cells can also exert a direct effector activity, which depends on intrinsic cytotoxic properties acquired and carried out along with the evolution of several pathogenic infections. The relevant role of CD4+ T cell lytic features in the control of such infectious conditions also leads to their exploitation as a new immunotherapeutic approach. This review aims at summarizing currently available data about functional and therapeutic relevance of cytotoxic CD4+ T cells in the context of viral infections and virus-driven tumors.