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.