γδ T cells confer protection against murine cytomegalovirus (MCMV).
Cytomegalovirus (CMV) is a leading infectious cause of morbidity in immune-compromised patients. γδ 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 αβ and/or γδ T cell-deficient mice, we here show that γδ T cells are as competent as αβ T cells to protect mice from CMV-induced death. γδ T cell-mediated protection involved control of viral load and prevented organ damage. γδ T cell recovery by bone marrow transplant or adoptive transfer experiments rescued CD3ε-/- mice from CMV-induced death confirming the protective antiviral role of γδ T cells. As observed in humans, different γδ 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- γδ T cells. NK cells were the largely preponderant producers of IFNγ and cytotoxic granules throughout the infection, suggesting that the protective role of γδ T cells did not principally rely on either of these two functions. Finally, γδ T cells were strikingly sufficient to fully protect Rag-/-γc-/- 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 γδ T cells, and open new perspectives for the characterization of a non classical mode of action which should foster the design of new γδ T cell based therapies, especially useful in αβ T cell compromised patients.
Université de Bordeaux, Bordeaux, France; CNRS, UMR 5164, Bordeaux, France.
Camille
C
Khairallah
Université de Bordeaux, Bordeaux, France; CNRS, UMR 5164, Bordeaux, France.
Sonia
S
Netzer
Université de Bordeaux, Bordeaux, France; CNRS, UMR 5164, Bordeaux, France.
Arnaud
A
Villacreces
Université de Bordeaux, Bordeaux, France; CNRS, UMR 5164, Bordeaux, France.
Marina
M
Juzan
Université de Bordeaux, Bordeaux, France; Laboratoire d'Immunologie et d'Immunogénétique, Animalerie A2, Bordeaux, France.
Benoît
B
Rousseau
Faculty of Pharmacy, Université Libre de Bruxelles (ULB), Brussels, Belgium.
Sara
S
Dulanto
Université de Bordeaux, Bordeaux, France; EA2406 Histologie et pathologie moléculaire des tumeurs, Bordeaux, France.
Alban
A
Giese
Université de Bordeaux, Bordeaux, France; Animalerie spécialisée, Bordeaux, France.
Pierre
P
Costet
Université de Bordeaux, Bordeaux, France; CNRS, UMR 5164, Bordeaux, France; Laboratoire d'Hématologie, Centre Hospitalo-Universitaire, Bordeaux, France.
Vincent
V
Praloran
Université de Bordeaux, Bordeaux, France; CNRS, UMR 5164, Bordeaux, France; Centre Hospitalo-Universitaire, Bordeaux, France.
Jean-François
JF
Moreau
Université de Bordeaux, Bordeaux, France; EA2406 Histologie et pathologie moléculaire des tumeurs, Bordeaux, France.
Pierre
P
Dubus
Faculty of Pharmacy, Université Libre de Bruxelles (ULB), Brussels, Belgium; Institute for Medical Immunology, Université Libre de Bruxelles (ULB), Brussels, Belgium.
David
D
Vermijlen
Université de Bordeaux, Bordeaux, France; CNRS, UMR 5164, Bordeaux, France.
Julie
J
Déchanet-Merville
Université de Bordeaux, Bordeaux, France; CNRS, UMR 5164, Bordeaux, France.
Myriam
M
Capone
D000818:Animals; D006566:Herpesviridae Infections / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D007111:Immunity, Cellular; D051379:Mice; D018345:Mice, Knockout; D018146:Muromegalovirus / Q000276:immunology*; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000235:genetics / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology* / Q000473:pathology
D016692:Receptors, Antigen, T-Cell, gamma-delta