Table 1.
Antiviral activity of γδ T cell subsets in in various experimental models
| 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 [IA−IE+] 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] |
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