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Table 1 Antiviral activity of γδ T cell subsets in in various experimental models

From: Role of γδ T cells in controlling viral infections with a focus on influenza virus: implications for designing novel therapeutic approaches

Viral infection Experimental model γδ subsets Antiviral mechanism References
HCV Co-cultures of Rep60 cells with either patients’ or healthy donors’ PBMC, or highly purified γδ T cells Vγ9Vδ2 Vγ9Vδ2 T cell-mediated IFN-γ-dependent anti-HCV activity [86]
HIV Infection of PBMCs of healthy donors with HIV Vγ9Vδ2 HIV replication inhibition as a result of releasing CCR5 ligand chemokines by activated Vγ9Vδ2 T cells [91]
PBMCs of healthy donors and HIV-1-infected patient, as well as HIV-1-infected PM1 cell line Vδ1 NKp30-induced Vδ1 T cell-mediated HIV-1 replication inhibition through β chemokines production [92]
Co-culture of γδ T cell-enriched from PBMCs of HIV+ and healthy donors with HIV-infected CD4+ T cells Vδ1+ A significant increase in Vδ1+ T cells expressing an activating NKG2C receptor in HIV-infected patients, compared with healthy donors
NKG2C-induced Vδ1+ T cell-mediated cytotoxicity in response to HIV infected- CD4 T cells expressing NKG2C ligand
A possible involvement of NKG2C-bearing Vδ1 T cells in reducing the number of CD4+ T cells observed in HIV+ persons with chronic untreated viraemia
[77]
Vδ1+ T cell-mediated killing of infected cells in a perforin-dependent mechanism [76]
A single cell line p815 coated with rabbit antibodies specific to p815 cells, as target cells accompanied by PBMs isolated from HIV+ and HIV donors, as effector cells Vγ2Vδ2 CD16-mediated ADCC by Vγ2Vδ2 T cells against antibody coated target cells
The potential capacity of CD16+ Vδ2+ T cells as potent ADCC effector cells to control HIV-1 disease progression
[78]
EBV Co-culture of Vγ9Vδ2 derived from seropositive EBV health donors’ PBMC with EBV-transformed autologous lymphoblastoid B cell lines (EBV-LCL)
Inoculation of EBV-LCL to humanized Rag2−/− γc−/− mice
Vγ9Vδ2 Cytotoxic activity of Vγ9Vδ2 T cells against EBV-LCL based on NKG2D triggering, as well as Fas/FasL- and TRAIL-mediated apoptosis
A possible involvement of IFN-γ in Vγ9Vδ2 T cell-mediated suppression of EBV-LCL proliferation in humanized mice
The potential function of Vγ9Vδ2 T cells in the control of EBV-induced lymphoproliferative disease (EBV/LPD) by killing of EBV-LCL in humanized mice
[79]
SIV Macaques model of SIV infection Vδ1/Vδ2 NKG2D-, IFN-γ-, and granzyme B-mediated antiviral activity of γδ T cells [93]
SARS-CoV Co-culture of Vγ9Vδ2 T cell lines isolated from PBMC of patient and healthy donors with SARS-CoV-infected THP-1 cells, a human monocyte cell line Vγ9Vδ2 Anti-SARS activity mediated by Vγ9Vδ2 T cells in an IFN-γ-dependent mechanism
The possible engagement of NKG2D in triggering the cytolytic activity of Vγ9Vδ2 T cells against SARS-CoV-infected cells
[94]
ZIKV Co-culture of ZIKV-infected A549 cells with PBMC of healthy donors Vδ2+ NKG2D-mediated perforin release by Vδ2+ T cells in response to ZIKV-infected virus expressing NKG2D ligands [80]
DV Co-cultures of autologous DV-infected dendritic cells with either patients’ or healthy donors’ PBMC, PBL, or purified γδ T cells pan γδ γδ T cell-mediated rapid anti-DV activity by producing IFN-γ and up-regulating CD 107a as a marker of degranulation
Monocyte-mediated enhancement of γδ T cell responses against DV-infected cells in an IL-18-dependent manner
[95]
HCMV Incubation of γδ T cell lines isolated from KTRs or healthy donors with IgG opsonized HCMV-infected fibroblasts Vδ2neg Co-operation of HCMV-induced CD16+ Vδ2neg T cells with anti-HCMV IgG recognizing infected cells to suppress virus propagation in an INF-γ-dependent mechanism
Synergistic effects of IL-12 and IFN-α produced during HCMV infection on the enhancement of CD16-induced IFN-γ secretion
[90]
Incubation of γδ T cell colons from patients’ or healthy donors’ PBMCs with models of HCMV infection in cell lines HLA- and NKG2D-unrestricted TCR-mediated recognition and killing of CMV-infected cells by Vδ2neg T cells in a perforin/granzyme B dependent pathway [96]
MCMV Normal and γδ T-cell-depleted mice Vγ1+ The ability of IFN-γ-producing Vγ1+ T cells to respond quickly to HSP65 induced at early phase of MCMV infection
A possible role of IL-12 and/or TNF-α produced during MCMV infection in increasing IFN-γ secretion by Vγ1+ T cells
[85]
WNV Normal, αβ- and γδ-TCR deficient mice pan-γδ IFN-γ-mediated antiviral immunity against WNV infection provided by γδ T cells
γδ T cell-induced perforin-mediated cytotoxicity
[75]
VV Normal, αβ- and γδ- TCR deficient mice pan-γδ The critical function of γδ T cells in mediating innate immunity by rapid recruitment to the site of infection, as well as by rapid response to VV infection in an IFN-γ dependent mechanism [83]
VSV Normal and T cell deficient mice pan-γδ A possible role of γδ T cells as an alternative pathway in antibody isotype switching from VSV-specific IgM to IgG in αβ T cell-deficient mice via an IFN-γ-dependent manner [82]
CNPV Vaccination of human volunteers with live recombinant CNPV Vγ9+ Expansion of CNP-specific IFN-γ-producing Vγ9+ T cells, as well as enhanced activity of NK cells (probably mediated by γδ T cells) in recipients of CNP vaccine
A possible contribution of γδ T cell- and NK-produced IFN-γ to develop protective type-1 memory immunity during primary immune responses
[97]
HSV-1 The mouse model for corneal infection with HSV-1 pan-γδ A dominant protective role for IFN-γ produced by γδ T cells, as well as macrophage-derived TNF-α and nitric oxide at early stages of HSV-1 infection
A possible role of γδ T cells and macrophages as the early line of defense during acute HSV-1 proliferation in reducing the recurrence rate of herpetic disease
[84]
HSV-induced cytotoxic activity of PBMCs from immune healthy donors and target cells Vγ9Vδ2 (< 80%) CD4 CD8 γδ T cell-mediated Killing of HSV-infected cells in an HLA-independent manner
A possible involvement of accessory molecules like LFA-1 as an enhancer of TCR signaling in γδ T cell-mediated cytotoxic activity
[98]
CVB3 C57BL/6, BI.Tg.Eα, and γδ knockout mice Vγ1+/Vγ4+ The contribution of γδ+ T cell subpopulations to host susceptibility to CVB3-induced myocarditis
MHC class II antigen (IA and IE) restricted clonal selection of Vγ subpopulations during thymic development
Promotion of CVB3-induced myocardial inflammation in BI.Tg.Eα [IAIE+] mice by Vγ4+ T cells-mediated Th1-biased immunity
T cell expressing Vγ1 gene-mediated suppression of CVB3-induced inflammatory damage in C57BL/6 [IA+IE] mice by modulating Th2-biased immunity
[99]
  1. HCV, Hepatitis C virus; Rep60, human hepatoma Huh7 cell line harboring HCV replicon; PBMCs, peripheral blood mononuclear cells; HIV, human immunodeficiency virus; MIP, macrophage inflammatory protein; RANTES, regulation on activation, normal T cell expressed and secreted; P815, mouse leukemia cell line; ADCC, antibody-dependent cellular cytotoxicity; EBV, Epstein–Bar virus; SARS-CoV, severe acute respiratory syndrome-associated coronavirus; ZIKV, Zika virus; DV, dengue virus; PBL, peripheral blood lymphocytes; HCMV, human cytomegalovirus; KTRs, kidney transplant recipients; HLA, human leukocyte antigen; MCMV, murine cytomegalovirus; HSP65, heat-shock protein 65; WNV, West Nile virus; VV, vaccinia virus; VSV, vesicular stomatitis virus; CNPV, canarypox virus; HSV-1, herpes simplex virus type 1; LFA-1, lymphocyte function-associated antigen-1; CVB3, coxsackievirus B3