gamma delta T Cells Confer Protection against Murine Cytomegalovirus (MCMV)

Camille Khairallah*, Sonia Netzer, Arnaud Villacreces, Marina Juzan, Benoit Rousseau, Sara Dulanto, Alban Giese, Pierre Costet, Vincent Praloran, Jean-Francois Moreau, Pierre Dubus, David Vermijlen, Julie Dechanet-Merville, Myriam Capone

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

Cytomegalovirus (CMV) is a leading infectious cause of morbidity in immune-compromised patients. gamma delta T cells have been involved in the response to CMV but their role in protection has not been firmly established and their dependency on other lymphocytes has not been addressed. Using C57BL/6 alpha beta and/or gamma delta T cell-deficient mice, we here show that gamma delta T cells are as competent as alpha beta T cells to protect mice from CMV-induced death. gamma delta T cell-mediated protection involved control of viral load and prevented organ damage. gamma delta T cell recovery by bone marrow transplant or adoptive transfer experiments rescued CD3e(-/-) mice from CMV-induced death confirming the protective antiviral role of gamma delta T cells. As observed in humans, different gamma delta T cell subsets were induced upon CMV challenge, which differentiated into effector memory cells. This response was observed in the liver and lungs and implicated both CD27(+) and CD27(-) gamma delta T cells. NK cells were the largely preponderant producers of IFN gamma and cytotoxic granules throughout the infection, suggesting that the protective role of gamma delta T cells did not principally rely on either of these two functions. Finally, gamma delta T cells were strikingly sufficient to fully protect Rag(-/-)gamma c(-/-) mice from death, demonstrating that they can act in the absence of B and NK cells. Altogether our results uncover an autonomous protective antiviral function of gamma delta T cells, and open new perspectives for the characterization of a non classical mode of action which should foster the design of new gamma delta T cell based therapies, especially useful in alpha beta T cell compromised patients.

Original languageEnglish
Article number1004702
Number of pages22
JournalPLoS Pathogens
Volume11
Issue number3
DOIs
Publication statusPublished - Mar 2015

Keywords

  • NATURAL-KILLER-CELLS
  • INTESTINAL EPITHELIAL-CELLS
  • ACUTE-LEUKEMIA PATIENTS
  • IMMUNE-RESPONSES
  • INTERFERON-GAMMA
  • MYELOID-LEUKEMIA
  • VIRUS-INFECTION
  • CMV SEROSTATUS
  • MUTANT MICE
  • TRANSPLANTATION

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