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Dissecting Innate Immune Signaling in Viral Evasion of Cytokine Production
Published on: March 2, 2014
γδ T cells confer protection against murine cytomegalovirus (MCMV)
Camille Khairallah1, Sonia Netzer1, Arnaud Villacreces1
1Université de Bordeaux, Bordeaux, France; CNRS, UMR 5164, Bordeaux, France.
Abstract:
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.
Insights
Gamma delta T cells protect against Cytomegalovirus (CMV) infection independently of other immune cells. These findings highlight gamma delta T cells
Area of Science:
- Immunology
- Virology
- Cellular Biology
Background:
- Cytomegalovirus (CMV) infection poses significant risks to immunocompromised individuals.
- The precise role of gamma delta (γδ) T cells in antiviral defense, particularly against CMV, remains incompletely understood.
- The interdependence of γδ T cells with other lymphocyte populations during CMV infection requires further investigation.
Purpose of the Study:
- To elucidate the protective capacity of γδ T cells against CMV-induced mortality.
- To determine whether γδ T cells can function autonomously in antiviral immunity.
- To explore the potential of γδ T cells in therapeutic strategies for CMV infections.
Main Methods:
- Utilized genetically modified mice deficient in αβ and/or γδ T cells to assess their roles in CMV infection.
- Employed bone marrow transplantation and adoptive T cell transfer to evaluate γδ T cell recovery and function.
- Analyzed γδ T cell subset differentiation, cytokine production, and cytotoxic activity in response to CMV challenge.
- Assessed the protective efficacy of γδ T cells in mice lacking B and NK cells (Rag-/-γc-/-).
Main Results:
- γδ T cells demonstrated a protective role comparable to αβ T cells against CMV-induced death.
- γδ T cell-mediated protection involved effective control of viral load and prevention of organ damage.
- CMV infection induced distinct γδ T cell subsets with effector memory phenotypes in the liver and lungs.
- γδ T cells provided complete protection against CMV-induced mortality even in the absence of B and NK cells.
Conclusions:
- γδ T cells possess an autonomous and potent antiviral function against CMV.
- The protective mechanism of γδ T cells against CMV does not primarily rely on NK cell-like functions (IFNγ and cytotoxic granules).
- These findings support the development of novel γδ T cell-based immunotherapies, particularly for patients with compromised αβ T cell immunity.
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