Control of Murine Cytomegalovirus Infection by γδ T Cells

Abstract

Infections with cytomegalovirus (CMV) can cause severe disease in immunosuppressed patients and infected newborns. Innate as well as cellular and humoral adaptive immune effector functions contribute to the control of CMV in immunocompetent individuals. None of the innate or adaptive immune functions are essential for virus control, however. Expansion of γδ T cells has been observed during human CMV (HCMV) infection in the fetus and in transplant patients with HCMV reactivation but the protective function of γδ T cells under these conditions remains unclear. Here we show for murine CMV (MCMV) infections that mice that lack CD8 and CD4 αβ-T cells as well as B lymphocytes can control a MCMV infection that is lethal in RAG-1-/- mice lacking any T- and B-cells. γδ T cells, isolated from infected mice can kill MCMV infected target cells in vitro and, importantly, provide long-term protection in infected RAG-1-/- mice after adoptive transfer. γδ T cells in MCMV infected hosts undergo a prominent and long-lasting phenotypic change most compatible with the view that the majority of the γδ T cell population persists in an effector/memory state even after resolution of the acute phase of the infection. A clonotypically focused Vγ1 and Vγ2 repertoire was observed at later stages of the infection in the organs where MCMV persists. These findings add γδ T cells as yet another protective component to the anti-CMV immune response. Our data provide clear evidence that γδ T cells can provide an effective control mechanism of acute CMV infections, particularly when conventional adaptive immune mechanisms are insufficient or absent, like in transplant patient or in the developing immune system in utero. The findings have implications in the stem cell transplant setting, as antigen recognition by γδ T cells is not MHC-restricted and dual reactivity against CMV and tumors has been described.

Emerging role of γδ T cells in vaccine‐mediated protection from infectious diseases

“…110 During secondary infection, cells proliferate and resolve infection Table 1. 111,112 These results suggest that cd T cells are important mediators of protection against CMV and support approaches using adoptive transfer of effector/memory cd T cells or targeting cd T cells in future CMV vaccine trials. 102 Several studies in mice have shown that (1) cd T cells are capable of protecting ab T-cell-deficient mice against CMV-induced pathology and (2) adoptive transfer of CMV-induced cd T cells provides long-term protection in immunodeficient mice.…”

Lymph Node Macrophages Restrict Murine Cytomegalovirus Dissemination

“…The detection of infected cells was facilitated by reporter viruses. For live imaging (MCMV-LUC), an HCMV IE1 promoterdriven luciferase expression cassette was inserted into m157 of a bacterial artificial chromosome (BAC)-cloned MCMV strain Smith genome that also was repaired for MCK2 expression (25). For fluorescent labeling of infected cells (MCMV-GR), an HCMV IE1 promoter-driven cassette was inserted into m157 of MCMV strain K181 by homologous recombination.…”

Human γδ T‐cell receptor repertoire is shaped by influenza viruses, age and tissue compartmentalisation

“…Suggestive evidence indicates that cd T cells are involved in diverse aspects of the host response, including acute and/or chronic inflammation, effective wound healing and the killing of virusinfected, cancerous and stressed cells. [1][2][3][4] In humans, cd T cells respond to chronic viral infections, as suggested by their robust proliferative capacity during EBV reactivation, 5 the upregulation of effector functions during HIV persistence, 6 increased CD69 expression and expansion of d1/d3 T cells in kidney transplant patients with associated CMV latency. 7 In addition, phosphoantigen-expanded human cd T cells upregulated IFN-c and cd T cells killed cells infected with human H1N1 and H5N1 influenza viruses.…”