organisation - the Instituto Gulbenkian de Ciência

ANTIGEN
PRESENTATION
AND T CELL ACTIVATION
Elisabetta Padovan Research Fellow
PhD in Immunology, University of Padova, Italy, 1994
Group Leader, Bern University Hospital, Switzerland
Principal Investigator at the IGC since 2006
T cells are central actors of antigen-specific immune responses and their function
is strongly influenced by the Antigen-presenting Cells (APC) they directly
interact with. APC control T cell activation also indirectly, by providing cytokines
that are induced by environmental triggers recognised by Pattern Recognition
Receptors (PRR). Although it has long been recognised that PRR on professional
APC instruct the cell fate decisions of naïve T lymphocytes, a careful analysis
of how PRR signalling modulates effector memory T cell function, directly and
indirectly through APC, is still missing. By studying the crosstalk between Monocyte/Macrophages
and T helper (Th) cells producing IL-17 (Th17) or IFN-γ (Th1)
we aim at dissecting how human Th17 and Th1 responses of healthy donors and
patients become tuned, also depending on the presence or absence of PRR
ligands.
HOW PATTERN RECOGNITION RECEPTORS (PRR) SIGNALLING CONTROLS
T LYMPHOCYTES ACTIVATION
Adaptive immunity depends on the induction of antigen-specific T cells in central
lymphoid organs, upon priming of naïve T cells by professional Antigen
Presenting Cells (APC) licensed through Toll-like Receptors (TLR). Up to now
it is still poorly known whether TLR signalling can also influence the crosstalk
between APC and CD4+ memory T cells, thus tuning T helper (Th) cell responses
in peripheral tissues. We use imaging techniques to resolve molecular events
occurring in living T cell/APC conjugates and dissect the modulatory effect of
TLR signalling on T cell immunity.
We have assessed the APC/T cell crosstalk established during antigen recognition.
The cytokine production pattern induced in Th17 cells activated by M1 and
M2 macrophages was assessed in 3D microscopy. Our imaging studies reveal
that IL-17 cytokine is contained in intracellular vesicles distributed around the
Microtubule Organising Centre (MTOC) of activated T cells, irrespective of the
type of APC (Figure 1 A). Quantitative analysis of our 3D images shows no differences
in the number of intracellular cytokine-containing vesicles and their
cytokine load.
COLLABORATORS
Perrine Paul-Gilloteaux (Institut Curie, Paris, France)
Claire Hivroz (Institut Curie, Paris, France)
A
B
CYTOKINE PRODUCTION PATTERN IN ACTIVATED TH17 CELLS.
A - 3D microscopy images show IL-17 (red) distributed around the T cell MTOC
(green) within a human Th17 clone recognising TSST-1 on M1 (left) and M2 (right)
Macrophages (blue). The quantitative analysis of up to 23 images plotted as total
number of IL-17 containing vesicles (top) and vesicles average fluorescence intensity
(bottom) is depicted in B.
IGC ANNUAL REPORT ‘11
RESEARCH FELLOWS
78