GRUPPI ADRIANA
Congresos y reuniones científicas
Título:
Study of Foxp3+ regulatory T cell responses during experimental Trypanosoma cruzi infection.
Autor/es:
ARAUJO CINTIA; TOSELLO BOARI, JIMENA; CANALE F; BECCARIA CG; FIOCCA VERNENGO F; GRUPPI ADRIANA; MONTES CAROLINA L; ACOSTA RODRIGUEZ E V
Lugar:
Mar del Plata
Reunión:
Jornada; LXII Reunión Anual de la Sociedad Argentina de Inmunología (Mar del Plata, Noviembre, 2014); 2014
Institución organizadora:
Sociedad Argentina de Inmunologia
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.
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.
