IMEX   05356
INSTITUTO DE MEDICINA EXPERIMENTAL
Unidad Ejecutora - UE
congresos y reuniones científicas
Título:
Influence of cathepsin L on CD4+ regulatory T cells peripheral homeostasis
Autor/es:
CAMICIA G; BADANO N; MAGGLIOCO AF; COSTA H; PIAZZON I; NEPOMNASCHY I
Lugar:
Buenos Aires
Reunión:
Congreso; First French-Argentine Immunology Congress; 2010
Institución organizadora:
Sociedad Argentina de Inmunologia
Resumen:
119.
Infuence of cathpesin-L on CD4+ regulatory T cells peripheral homeostasis
Camicia, Gabriela; Badano,
Noel; Maglioco, Andrea; Costa, Héctor;Piazzon, Isabel; Nepomnaschy, Irene
ILEX-CONICET, División
Medicina Experimental, IIHEMA, Academia
Nacional de Medicina de
Buenos Aires.
gabrielacamicia@yahoo.com.ar
CD4+CD25+Foxp3+
regulatory T cells play a pivotal role in the
maintenance
of peripheral tolerance and immune homeostasis.
We
had previously shown that cathepsin-L de*cient mice
(CTSLnkt)
show increased absolute number of CD4+ regulatory
T
cells in peripheral lymph nodes (LN) whereas the number of
CD4+Foxp3+
thymic cells was shown to be decreased. In this
study,
we investigated the impact of cathepsin-L on CD4+ regulatory
T
cell peripheral homeostasis by analyzing CD4+CD25+
(Treg)
cell turnover in CTSLnkt mice. To determine the proliferation
rate
of LN Treg subsets, 5-bromo-2- deoxyuridine (BrdU)
was
injected for 7 days. FACS analysis showed that both the
CTSLnkt
Treg and CD4+CD25- subsets showed a signi*cant increase
in
the % of BrdU+ cells as compared to wild type (mean
%
BrdU+/Treg cells ± DS: 22±3 vs 12±1, p<0.005, n=4. Mean %
BrdU+/CD4+CD25-
cells ± DS: 10±1 vs 4.0±0.1, p<0.001, n=4). To
evaluate
the % of Treg cells undergoing apoptosis annexin V
staining
was used. An increase both in the % of apoptotic Treg
and
CD4+CD25- cells was observed in the LN of mutant mice
(mean
% annexin V+/Treg cells ± DS: 53±3 vs 43±3, p<0.005,
n=4.
Mean % annexin V+/CD4+CD25- cells ± DS: 35±2 vs 25±2,
p<0.001,
n=4). Notably, both mutant and wild type Treg subsets
showed
increased apoptosis as compared to their CD4+CD25-
counterparts.
Our results show that the CTSLnkt mutation
causes
increases in the proliferation but also in the apoptosis
levels
of both Treg and CD4+CD25- cells. The fact that mutant
Treg
and CD4+CD25- cells showed increases in proliferation but
also
in the apoptosis levels, does not support that di'erences in
the
proliferation vs apoptosis balance of Treg may be involved
in
the increases of peripheral Treg numbers in CTSLnkt mice,
thus
raising the possibility that conversion of CD4+CD25- into
CD4+CD25+
cells could be involved. In support of this hypothesis,
increased
levels of TGF-\ were found in cultures of LN CTSLnkt
cells
using both RT-PCR and ELISA assays.