Characterization of a Unique γδ T-Cell Subset as a Specific Marker of Cytomegalovirus Infection Severity. (5th July 2020)

• Record Type: Journal Article
• Authors: Kaminski, Hannah; Ménard, Coline; El Hayani, Bouchra; Adjibabi, And-Nan; Marsères, Gabriel; Courant, Maxime; Zouine, Atika; Pitard, Vincent; Garrigue, Isabelle; Burrel, Sonia; Moreau, Jean-François; Couzi, Lionel; Visentin, Jonathan; Merville, Pierre; Déchanet-Merville, Julie
• Is Part Of: Journal of infectious diseases. Volume 223:Number 4(2021)
• Page Start: 655
• Page End: 666
• Publication Date: 2020-07-05
• Subjects: gamma-delta T cells -- kidney transplant recipients -- CMV infection; Communicable diseases -- Periodicals; Diseases -- Causes and theories of causation -- Periodicals; Medicine -- Periodicals; Communicable Diseases -- Periodicals; Electronic journals; 616.9
• DOI: 10.1093/infdis/jiaa400
• Languages: English
• ISSNs: 0022-1899

Abstract

Abstract: Cytomegalovirus (CMV) is a major infectious cause of death and disease after transplantation. We have previously demonstrated that the tissue-associated adaptive Vδ2 neg γδ T cells are key effectors responding to CMV and associated with recovery, contrasting with their innatelike circulating counterparts, the Vγ9 pos Vδ2 pos T cells that respond to phosphoantigens but not to CMV. A third Vγ9 neg Vδ2 pos subgroup with adaptive functions has been described in adults. In the current study, we demonstrate that these Vγ9 neg Vδ2 pos T cells are also components of the CMV immune response while presenting with distinct characteristics from Vδ2 neg γδ T cells. In a cohort of kidney transplant recipients, CMV seropositivity was the unique clinical parameter associated with Vγ9 neg Vδ2 pos T-cell expansion and differentiation. Extensive phenotyping demonstrated their substantial cytotoxic potential and activation during acute CMV primary infection or reinfection. In vitro, Vγ9 neg Vδ2 pos T cells responded specifically to CMV-infected cells in a T-cell receptor–dependent manner and through strong interferon γ production. Finally, Vγ9 neg Vδ2 pos T cells were the only γδ T-cell subset in which expansion was tightly correlated with the severity of CMV disease. To conclude, our results identify a new player in the immune response against CMV and open interesting clinical perspectives for using Vγ9 neg Vδ2 pos T cells as an immune marker for CMV disease severity in immunocompromised patients. Abstract : A newly described component of the immune response against cytomegalovirus (CMV), Vγ9 neg Vδ2 pos T cells show direct, specific, and T-cell receptor–dependent recognition of CMV-infected cells and are the only γδ T-cell subset with expansion tightly correlated with CMV disease severity.