Activated human renal tubular cells inhibit autologous immune responses

Wilkinson, Ray, Wang, Xiangju, Roper, Kathrein E. and Healy, Helen (2011) Activated human renal tubular cells inhibit autologous immune responses. Nephrology, Dialysis, Transplantation, 26 5: 1483-1492.


Author Wilkinson, Ray
Wang, Xiangju
Roper, Kathrein E.
Healy, Helen
Title Activated human renal tubular cells inhibit autologous immune responses
Journal name Nephrology, Dialysis, Transplantation   Check publisher's open access policy
ISSN 0931-0509
1460-2385
Publication date 2011-05-26
Year available 2010
Sub-type Article (original research)
DOI 10.1093/ndt/gfq677
Volume 26
Issue 5
Start page 1483
End page 1492
Total pages 10
Place of publication Oxford, United Kingdom
Publisher Oxford University Press
Collection year 2011
Language eng
Formatted abstract Background. Renal proximal tubule epithelial cells (PTEC)
respond and contribute to the pathological process in a range
of kidney diseases. Within this disease setting, PTEC upregulate
surface antigens which may enable them to act as
non-professional antigen-presenting cells and become targets
for infiltrating T cells in the context of disease and allograft
rejection. In order to define, for the first time, whether
PTEC modulate immune responses within the autologous
human system, we monitored their interaction with T and
B cells in the presence of stimuli which mimic immunological
signalling.
Methods. The expression of PTEC surface antigen in response
to inflammatory mediators was monitored by flow
cytometry. Purified T and B lymphocyte subsets and peripheral
blood mononuclear cells were cultured in the presence
or absence of autologous activated PTEC, and their
responses to specific activators were monitored by proliferation,
cytokine secretion and surface antigen expression.
Some experiments were performed in the presence of
blocking antibodies to PD-L1.
Results. The presence of activated primary autologous
PTEC resulted in significantly decreased T- and B-cell proliferative
responses, which were only partly mediated by
programmed death ligand 1. This modulation was not induced
by a decrease in activation markers or an increase
in T regulatory cells but was accompanied by strong significant
skewing of cytokine profiles. Significant decreases in
gamma-interferon, interleukin-2 and tumour necrosis factor
and increases in interleukin-4 were detected in the presence
of PTEC, indicating that these cells induce a shift away from
an inflammatory Th1 effector profile to a Th2 type profile.
Conclusion. Human PTEC do modulate autologous immune
responses. We hypothesize that such mechanisms
may have developed to help dampen inflammatory responses
and macrophage activation seen within kidney interstitium
in many immune-mediated kidney diseases.
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ
Additional Notes First published online: November 2, 2010

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2011 Collection
School of Medicine Publications
 
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Created: Mon, 28 Mar 2011, 13:57:35 EST by Debbie Banks on behalf of School of Medicine