Cytotoxic CD4 T Cells-Friend or Foe during Viral Infection?
CD4 T cells with cytotoxic function were once thought to be an artifact due to long-termin vitrocultures but have in more recent years become accepted and reported in the literature in response to a number of viral infections. In this review, we focus on cytotoxic CD4 T cells in the context of human viral infections and in some infections that affect mice and non-human primates. We examine the effector mechanisms used by cytotoxic CD4 cells, the phenotypes that describe this population, and the transcription factors and pathways that lead to their induction following infection. We further consider the cells that are the predominant targets of this effector subset and describe the viral infections in which CD4 cytotoxic T lymphocytes have been shown to play a protective or pathologic role. Cytotoxic CD4 T cells are detected in the circulation at much higher levels than previously realized and are now recognized to have an important role in the immune response to viral infections.
Department of Microbiology and Immunology, Peter Doherty Institute, University of Melbourne , Melbourne, VIC , Australia.
Jennifer A
JA
Juno
Immunovirology and Pathogenesis Program, The Kirby Institute for Infection and Immunity in Society, University of New South Wales Australia , Sydney, NSW , Australia.
David
D
van Bockel
Department of Microbiology and Immunology, Peter Doherty Institute, University of Melbourne, Melbourne, VIC, Australia; Melbourne Sexual Health Centre, Department of Infectious Diseases, Alfred Health, Central Clinical School, Monash University, Melbourne, VIC, Australia; ARC Centre of Excellence in Convergent Bio-Nano Science and Technology, University of Melbourne, Parkville, VIC, Australia.
Stephen J
SJ
Kent
Immunovirology and Pathogenesis Program, The Kirby Institute for Infection and Immunity in Society, University of New South Wales Australia, Sydney, NSW, Australia; St Vincent's Hospital, Sydney, NSW, Australia.
Anthony D
AD
Kelleher
Immunovirology and Pathogenesis Program, The Kirby Institute for Infection and Immunity in Society, University of New South Wales Australia, Sydney, NSW, Australia; St Vincent's Hospital, Sydney, NSW, Australia.
John J
JJ
Zaunders
Immunovirology and Pathogenesis Program, The Kirby Institute for Infection and Immunity in Society, University of New South Wales Australia , Sydney, NSW , Australia.
C Mee Ling
CM
Munier
CD4; CMV; EBV; HIV; cytotoxic; granzyme; influenza; perforin