Important Role of gd T Cells in Anti-SARS-CoV-2 Immune Response
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Gumrukcu, Serhat & Singh, Spriha & Howell, Gregory & Musikanth, Phillip & Nguyen, Tung. (2020). Important Role of gd T Cells in Anti-SARS-CoV-2 Immune Response. 10.13140/RG.2.2.20314.98243. We evaluated the SARS-CoV-2-specific antiviral activities of gamma-delta T cells isolated from COVID-19 convalescent individuals
BACKGROUND
• COVID-19 is the most devastating pandemic in this century.
• Inconsistent and short-lived antibody responses to the infection are
concerning, especially for the vaccine efficacy expectations.
• It has been shown that gamma-delta (gd) T cells played a significant role in
past SARS epidemics.
• We hypothesized that cellular immunity could also play a major role in SARSCoV-
2 infection.
• We evaluated the SARS-CoV-2-specific antiviral activities of gd T cells isolated
from COVID-19 convalescent individuals and
METHODS
• Ten individuals with confirmed COVID-19 infection within the past 90 days of
recruitment and seven seronegative individuals were recruited to the study.
(Fig 1)
• Cell-mediated immune responses were evaluated by screening all PBMC
subsets by flow cytometry, including alpha-beta (ab) and gd T-cell receptor
(TCR) repertoires using 24 TCR Vb and 3 TCR Vd chain-specific monoclonal
antibodies (MAbs).
• Pre-infection PBMCs from 3 out of 10 trial subjects were also compared to
their respective post-infection samples by immunophenotyping via flow
cytometry.
• Pre- and post-infection gd T cells were expanded ex vivo in the presence or
absence of 100nM recombinant SARS-CoV-2 spike (S) protein and evaluated
for expansion rate, purity and CD45RA-CD27-effector memory (EM) and
CD45RA-CD27+ central memory (CM) subset percentages.
• On day 3 of expansion, supernatants were analyzed by a flow-based multiplex
assay to quantify IL-2, IL-4, IL-10, IL-6, IL-17A, TNF-
RESULTS
• Analyses of the immunophenotyping and T cell repertoires in all ten
convalescent patients revealed that gd T cell populations were activated
during the infection.
• The comparison between pre- and post-infection immune cell profiles in
several subjects demonstrated that certain memory subsets of Vg9Vd2 T cell
populations were also selectively expanded (Fig 2)
• 250%, 975%, and 617% absolute count increase observed in gd T, Vd2 EM,
and Vd2 CM cells respectively.
• Ex vivo expansion of pre- and post-infection gd T cells in the presence or
absence of S protein revealed substantial expansion of EM and CM gd T cells
in the post-infection PBMC cultures supplemented with S protein compared
to other groups. (Fig 3)
• Multiplex cytokine analyses showed increases in IFN-g, IL-10, granzyme A,
granzyme B, perforin and granulysin in gd T cell cultures supplemented with S
protein compared to other groups. (Fig 4)
DISCUSSION
• Substantial increases in gd T cell populations were observed in post-COVID-19
PBMCs compared to pre-COVID19 and seronegative samples.
• gd T cells robustly expanded ex vivo in the presence of S protein demonstrated
enhanced levels of central memory and effector memory cells.
• Ex vivo expanded gd T cells also demonstrated increased levels of IL-10, IFN-g,
Perforin, Granulysin, Granzyme A and Granzyme B.
• Demographics of convalescent and seronegative trial participants.
• Pre- and post-infection samples from participants #1, #2, and #3 were evaluated
CONCLUSION
• There are dozens of different vaccines and treatments currently being
developed for COVID-19.
• Inconsistent and short-lived antibody responses in some of the recovered
individuals are concerning.
• gd T cells are known to play an important role in cellular immunity against
SARS infection
• We established that these cells also play a role against SARS-CoV-2 by
demonstrating their enhanced expansion rates in the presence of viral
protein S.
• Moreover, these ex vivo expanded gd T cells demonstrated memory cell
properties, suggesting an important role of gd T cells in sustained immunity
against SARS-CoV-2.