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Immunology 2018
J u l y 0 5 - 0 7 , 2 0 1 8
V i e n n a , A u s t r i a
Page 60
Journal of Clinical Immunology and Allergy
ISSN 2471-304X
1 5
t h
I n t e r n a t i o n a l C o n f e r e n c e o n
Immunology
R
eactive oxygen species (ROS) are known to influence the outcome
of T cell responses. Depending on concentration, exposure time, and
microenvironment, the effects of ROS on T cells can be very distinct and affect
a variety of physiological events, including cell proliferation, host defense,
differentiation, apoptosis, senescence, and activation of growth-related
signaling pathways. T cells can produce low levels of H
2
O
2
upon TCR and
chemokine stimulation, which have been shown to facilitate T cell activation.
Additionally, T lymphocytes also express NADPH oxidase enzymes NOX
2
and
DUOX1 that catalyze the reduction of molecular oxygen to generate superoxide
O
2
, which can dismute to generate ROS species. These ROS participate
in host defense by killing or damaging invading microbes. Additionally, in
several human pathologies, including cancer and a variety of auto- immune
disorders, high levels of pro-oxidants are known to induce T lymphocyte hypo
responsiveness. H
2
O
2
is an early danger cue required for innate immune cell
recruitment to wounds, but little is known about the effect of H
2
O
2
on migration
of human adaptive immune cells to sites of inflammation. However, oxidative
stress is known to impair T cell activity, induce actin stiffness, and inhibit cell
polarization. In this study, we show that H
2
O
2
selectively impedes chemokinesis
and chemotaxis of previously activated human T cells to CXCL11, but not other
chemokines. This deficiency in migration is due to a reduction in inflammatory
chemokine receptor CXCR3 surface expression and cellular activation of
lipid phosphatase SHIP-1. Moreover, pharmacological evidence indicates
that H
2
O
2
acts via a Src kinase to activate the lipid phosphatase SHIP-1,
a negative regulator of PI3K signaling. Thus, while H
2
O
2
can function as an
early recruitment trigger for innate immune cells, it appears to operate as an
inhibitor of T lymphocyte immune adaptive responses that are not required
until later in the repair process.
Biography
Stephen Ward is Head of Pharmacy and Pharmacology at the
University of Bath and has held several personal fellowships
and received funding from the Wellcome Trust, MRC, BBSRC
and Royal Society. He has published over 110 primary research
articles and reviews in the field of Inflammatory Cell Biology and
has supervised over 35 PhD students. This research has often
involved close collaboration with industry that has enhanced
student training by allowing them to spend time in industrial
laboratories.
S.G.Ward@bath.ac.ukHydrogen peroxide triggers a dual signaling axis to selectively
suppress CXCL11/CXCR3 –activated human T lymphocyte migration
Jennifer A Ball
1
, Will Wood
2
and Stephen G Ward
1
1
University of Bath, UK
2
University of Bristol, UK
Stephen G Ward et al., Insights Allergy Asthma Bronchitis 2018, Volume: 4
DOI: 10.21767/2471-304X-C1-002