INVESTIGADORES
MONTES Carolina Lucia
congresos y reuniones científicas
Título:
Study of FOXP3+ regulatory T cell responses during experimental T cruzi infection
Autor/es:
ARAUJO-FURLAN C; TOSELLO BOARI J; CANALE F; BECCARIA, CRISTIAN G;; FIOCCA VEMENGO F; GRUPPI A; MONTES CL; ACOSTA RODRIGUEZ EV
Reunión:
Congreso; LIX Reunión Científica Anual de la Sociedad Argentina de Investigación Clínica. LXII Reunión Anual de la Sociedad Argentina de Inmunologia; 2014
Institución organizadora:
SAI-SAIC
Resumen:
CD4+CD25+Foxp3+ regulatory T cells (TR) have a dual role
during infections as they limit immunopathology but also restrain
immunity to the pathogen. Regulatory responses during T. cruzi
(Tc) infection have been poorly characterized and TR role remains
controversial. Previous results show that TR frequency is reduced
in periphery upon Tc infection and that TR show upregulation of
PD1, CTLA4, CD103 and CXCR3 expression. Here, we aimed at
elucidating the causes of TR frequency reduction and studying
the effector function and biological relevance of TR during Tc
infection. Using Foxp3-GFP reporter mice, we determined that
apoptosis of TR was increased upon infection but to a similar
extent than in conventional CD4 T cells (TC), ruling out disproportionate
death as cause of the reduced TR frequency. Next, we
evaluated generation of inducible TR (iTR) by adoptive transfer of
CD4+CD25-GFP- TC into WT hosts. High% of iTR was detected
in mesenteric lymph nodes of transferred non-infected (NI) mice,
but this% was diminished in infected (INF) mice, suggesting a
reduced generation of iTR during Tc infection. In agreement, the%
of TR expressing Neuropilin1 and Helios (natural TR markers)
was increased in periphery. As TR show activation signs that
may correlate with enhanced suppressive capacity, we tested TR
function by conventional in vitro suppression assays. Proliferation
analysis showed that TR purified from NI and INF mice showed a
similar suppressive capacity, indicating a conserved TR function.
To address the biological relevance of the reduced TR frequency,
we treated INF mice with all-trans retinoic acid (atRA) that
increases TR numbers modulating TR/Th17 balance. In vivo atRA
treatment did not increase the% of TR in any organ from INF mice.
Though, in vitro atRA treatment of naïve TC cells from NI or INF
mice generated large numbers of iTR. Currently we are studying
stability and function of atRA iTR and their possible therapeutic
use to modulate Tc infection.