Single dose intranasal administration of retinal autoantigen generates a rapid accumulation and cell activation in draining lymph node and spleen: implications for tolerance therapy
Andrew D Dicka b, Vijay Sharmaa, Janet Liversidgea
a Division of
Ophthalmology, University of Aberdeen, UK, b Department of
Ophthalmology, University of Bristol, UK
Correspondence to: Professor Andrew D Dick, Division of Ophthalmology, Bristol Eye Hospital, Lower Maudlin Street, Bristol BS1 2LX, UK a.dick{at}bristol.ac.uk
Accepted for publication 2 April 2001
BACKGROUND/AIMS
A
single intranasal delivery of retinal autoantigen suppresses
effectively experimental autoimmune uveoretinitis (EAU). To further
unravel underlying mechanisms the authors wished to determine, firstly,
the kinetics of antigen delivery and, secondly, the early cellular
responses involved in the initial stages of nasal mucosal tolerance induction.
METHODSFlow
cytometry, cell proliferation assays, and microscopy were used to track
antigen following a single, intranasal dose of Alexa-488 labelled
retinal antigen.
RESULTSA rapid
accumulation of antigen within both superficial cervical lymph nodes
(SCLN) and spleen was observed after 30 minutes. Significant
proliferative responses to IRBP were elicited by 48 hours indicating
that systemic priming of naive T cells to retinal antigen had occurred.
Cell activation was further confirmed by immunoprecipitation studies,
which demonstrated phosphorylation of STAT4 but not STAT6 in both lymph
nodes and spleen. However, at 24 hours, STAT4 heterodimerisation with
STAT 3 was only observed in spleen.
CONCLUSIONSThe
results provide novel evidence that following a single intranasal
application rapid transfer of antigen occurs. Resulting T cell
proliferation develops consequent to differential cell signalling in
SCLN and spleen. Further understanding of these underlying cellular
mechanisms, in particular as is inferred by the results the
contribution of local versus systemic tolerance induction, may assist
in strategies to clinically apply mucosal tolerance therapy successfully.
© 2001 by British Journal of Ophthalmology
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