A dual nature of γδ T cell immune memory responses

  1. Tsz Kin Suen
  2. Burcu Al
  3. Alice Scarpa
  4. Anca Dorhoi
  5. Mihai G Netea
  6. Katarzyna Placek  Is a corresponding author
  1. Immunology and Metabolism Unit, Life and Medical Sciences (LIMES) Institute, University of Bonn, Germany
  2. Institut of Immunology, Friedrich-Loeffler-Institut, Federal Research Institute for Animal Health, Germany
  3. Department of Internal Medicine and Radboud Center for Infectious Diseases, Radboud University Medical Center, Netherlands
1 figure and 1 table

Figures

Schematic representation of adaptive vs. innate immune memory characteristics.

Myeloid cells and lymphocytes mount immune memory responses characterized by the enhanced effector function upon secondary exposure. While innate immune cells produce more inflammatory cytokines upon secondary challenge with heterologous stimuli, adaptive memory immune cells rapidly proliferate and generate copious amounts of antibodies and cytokines upon rechallenge with the same antigen. Antibodies, as well as memory B cells and T cells, persist in the host while cytokines produced by innate immune cells return to the baseline after the resolution of infection. Innate immune memory lasts relatively shorter than adaptive immune memory. Both adaptive and innate immune memory formation is accompanied by epigenetics and metabolic rewiring, facilitating transcriptional responses and allowing more robust immune reactions upon secondary challenge. TCR: T-cell receptor, BCR: B-cell receptor. Created with BioRender.com.

Tables

Table 1
Immune memory responses of gamma delta (γδ) T cells.

BCG: Bacille Calmette-Guerin; CMV: Cytomegalovirus; HSV: herpes simplex virus; IMQ: imiquimod; MMR: measles-mumps-rubella; MPV: Mpox virus.

SpeciesT cell subsetExperimental settingLocationAdaptive immune memory responsesInnate immune memory responsesRef
Inducing agentImmune memory response characteristicsInducing agentImmune memory response characteristics
Human and non-human primatesVδ2In vitroPeripheral bloodBCGEnhanced proliferation upon M. tuberculosis stimulationHoft et al., 1998; Kabelitz et al., 1991
Vδ2In vivoPeripheral bloodBCGEnhanced proliferation and IFN-γ production upon restimulationKabelitz et al., 1991
γδIn vivoPulmonary and peripheral bloodBCGEnhanced proliferation upon reinfectionShen et al., 2002; Lai et al., 2003
Vδ2In vivoPeripheral bloodListeria monocytogenesEnhanced proliferation and effector function upon reinfectionRyan-Payseur et al., 2012
γδIn vivoPeripheral bloodPlasmodium falciparumEnhanced proliferation and IFN-γ production upon restimulationTeirlinck et al., 2011
Vδ1In vivoPeripheral bloodPlasmodium falciparumClonal expansion, recurrent parasite-exposure driven expansion and differentiationvon Borstel et al., 2021; Rutishauser et al., 2020
Vδ2In vivoPeripheral bloodSARS-CoV-2 mRNA vaccineEnhanced proliferation and IFN-γ production upon revaccinationTerzoli et al., 2024
Vδ2In vivoPeripheral bloodMPVEnhanced proliferation and IFN-γ production upon rechallengeShao et al., 2009
Vδ1In vivoPeripheral bloodCMVRapid proliferation and infection resolution after reinfectionPitard et al., 2008
Vδ2In vivoPulmonary compartmentListeria monocytogenesEnhanced IFN-γ and perforin production; lower pulmonary pathology and less weight loss upon M. tuberculosis infectionShen et al., 2019
γδIn vitroPeripheral bloodBCGEnhanced TNF and IFN-γ production upon C. albican challenge; transcriptional rewiringSuen et al., 2024
Vδ2In vitroPeripheral bloodHSVEnhanced lysing ability of infected cells upon PHA or mycobacteria stimulationBukowski et al., 1994
γδIn vitroPeripheral bloodMMREnhanced TNF and IFN-γ production upon CD3 stimulation; transcriptional and metabolic rewiringRöring et al., 2024
MouseVγ4Vδ1In vivoIntestinal mucosaListeria monocytogenesEnhanced proliferation and infection clearance upon rechallengeSheridan et al., 2013
Vγ4In vivoIntestinal epitheliumListeria monocytogenesEnhanced IL-17 production and clustering with L monocytogenes replication foci upon secondary infectionRomagnoli et al., 2016
Vγ6In vivoPeritoneum, draining mediastinal lymph nodesStaphylococcus aureusEnhanced IL-17 production and infection clearance after reinfectionMurphy et al., 2014
Vγ6In vivoKidneyStaphylococcus aureusReduced renal bacterial load upon reinfectionBertram et al., 2023
Vγ1In vivoLiver, lung, spleenMCMVEnhanced proliferation and survival rate upon rechallengeKhairallah et al., 2015
γδIn vitroLiver, spleenPlasmodium chabaudiEnhanced CD107a expression and IFN-γ production upon rechallenge; transcriptional reprogrammingKumarasingha et al., 2020
Vγ4Vδ4In vivoSkinIMQEnhanced proliferation and IL-17 production upon IMQ rechallengeRamírez-Valle et al., 2015
Vγ4Vδ4In vivoSkin; earIMQEnhanced proliferation and IL-17 production and neutrophil recruitment upon IMQ rechallengeHartwig et al., 2015
Vγ4Vδ1In vitroGut; bulk mesenteric lymph nodesListeria monocytogenesEnhanced proliferation and IFN-γ and IL-17A production upon S. enterica serovar Typhimurium and C. rodentium challengeKhairallah et al., 2022
CowγδIn vitroAirway and peripheral bloodBCGIncreased IFN-γ producing γδ T cellsGuerra-Maupome and McGill, 2019
γδIn vitroPeripheral bloodBCGEnhanced IL-6 and TNF production upon Escherichia coli, LPS and Pam3CSK4 stimulation; epigenetic rewiringSamuel et al., 2024

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  1. Tsz Kin Suen
  2. Burcu Al
  3. Alice Scarpa
  4. Anca Dorhoi
  5. Mihai G Netea
  6. Katarzyna Placek
(2025)
A dual nature of γδ T cell immune memory responses
eLife 14:e104887.
https://doi.org/10.7554/eLife.104887