INVESTIGADORES
MAGLIOCO Andrea Florencia
congresos y reuniones científicas
Título:
CTSL FROM FIBROBLASTIC RETICULAR LYMPH NODE CELLS NEGATIVELY REGULATES CONVERSION OF CD4 CELLS TO THE TREG CELL PHENOTYPE
Autor/es:
MAGLIOCO A; CAMICIA G; BADANO N; COSTA H; CAMERANO G; PIAZZON I; NEPOMNASCHY I
Reunión:
Congreso; LIX Reunion anual de SAIC-LXII Reunion anual de SAI; 2014
Institución organizadora:
Saic-SAI
Resumen:
Cathepsin L (CTSL) is a lysosomal cysteine peptidase with
diverse and highly specific functions. We and others have shown
that CTSL is involved in thymic CD4+ T-cell positive selection.
Using CTSLnkt/nkt mice that lack CTSL activity we have previously
demonstrated that the absence of CTSL activity correlates with
increases both in the number of lymph node (LN) and spleen
CD4+CD25+Foxp3+ (Treg) cells and in the ratio between CD4+
Treg and CD4+CD25-Foxp3- (T conv) cells within CD4+ cells.
Contrarily, CTSLnkt/nkt and wt mice show no differences both in the
number of thymic CD4+CD8- Foxp3+ cells or in the ratio between
Treg and Tconv cells within CD4+CD8- thymocytes, suggesting
that the increase in the number of LN Treg cells is established
number of thymic CD4+CD8- Foxp3+ cells or in the ratio between
Treg and Tconv cells within CD4+CD8- thymocytes, suggesting
that the increase in the number of LN Treg cells is established
demonstrated that the absence of CTSL activity correlates with
increases both in the number of lymph node (LN) and spleen
CD4+CD25+Foxp3+ (Treg) cells and in the ratio between CD4+
Treg and CD4+CD25-Foxp3- (T conv) cells within CD4+ cells.
Contrarily, CTSLnkt/nkt and wt mice show no differences both in the
number of thymic CD4+CD8- Foxp3+ cells or in the ratio between
Treg and Tconv cells within CD4+CD8- thymocytes, suggesting
that the increase in the number of LN Treg cells is established
number of thymic CD4+CD8- Foxp3+ cells or in the ratio between
Treg and Tconv cells within CD4+CD8- thymocytes, suggesting
that the increase in the number of LN Treg cells is established
nkt/nkt mice that lack CTSL activity we have previously
demonstrated that the absence of CTSL activity correlates with
increases both in the number of lymph node (LN) and spleen
CD4+CD25+Foxp3+ (Treg) cells and in the ratio between CD4+
Treg and CD4+CD25-Foxp3- (T conv) cells within CD4+ cells.
Contrarily, CTSLnkt/nkt and wt mice show no differences both in the
number of thymic CD4+CD8- Foxp3+ cells or in the ratio between
Treg and Tconv cells within CD4+CD8- thymocytes, suggesting
that the increase in the number of LN Treg cells is established
number of thymic CD4+CD8- Foxp3+ cells or in the ratio between
Treg and Tconv cells within CD4+CD8- thymocytes, suggesting
that the increase in the number of LN Treg cells is established
nkt/nkt and wt mice show no differences both in the
number of thymic CD4+CD8- Foxp3+ cells or in the ratio between
Treg and Tconv cells within CD4+CD8- thymocytes, suggesting
that the increase in the number of LN Treg cells is established
in the periphery of mutant mice. Herein we analyzed whether
conversion is involved in the increase in the Treg peripheral cell
number in CTSLnkt/nkt mice and the involvement of LN stromal
cells (LNSC). LN CD4+CD25-Foxp3-cells activated with anti-CD3,
anti-CD28 and IL-2 but without exogenous TGF-â1 were cultivated
with supernatants (sn) from mutant or wt LNSC. Conversion was
with supernatants (sn) from mutant or wt LNSC. Conversion was
cells (LNSC). LN CD4+CD25-Foxp3-cells activated with anti-CD3,
anti-CD28 and IL-2 but without exogenous TGF-â1 were cultivated
with supernatants (sn) from mutant or wt LNSC. Conversion was
with supernatants (sn) from mutant or wt LNSC. Conversion was
nkt/nkt mice and the involvement of LN stromal
cells (LNSC). LN CD4+CD25-Foxp3-cells activated with anti-CD3,
anti-CD28 and IL-2 but without exogenous TGF-â1 were cultivated
with supernatants (sn) from mutant or wt LNSC. Conversion was
with supernatants (sn) from mutant or wt LNSC. Conversion was
â1 were cultivated
with supernatants (sn) from mutant or wt LNSC. Conversion was
significantly increased by the addition of mutant vs wt LNSCsn
(i.e. percentage of Treg cells in CTSLnkt/nkt Tconv cells cultured
with mutant or wt LNSCsn: 15.8±2 vs 7.3±1.2, n=3, p<0.01).
with mutant or wt LNSCsn: 15.8±2 vs 7.3±1.2, n=3, p<0.01).
nkt/nkt Tconv cells cultured
with mutant or wt LNSCsn: 15.8±2 vs 7.3±1.2, n=3, p<0.01).
These Treg percentages significantly diminished in the presence
of a TGF-â1 inhibitor. The mutant LNSC produced more TGF-â1â1 inhibitor. The mutant LNSC produced more TGF-â1
than that of wt mice (mutant vs wt LNSC sn, in pg/ml: 1618±198
vs 245±12.3, p>0.01, n=3; measured by ELISA). More than 97%
of both mutant and wt LN stromal cell lines were gp38 + CD35-
CD21-, indicating a fibroblastic reticular phenotype. These resu lts
indicate that conversion can play a role in the increase of Treg
cells in the periphery of CTSLnkt/nkt mice, being TGF-â productionnkt/nkt mice, being TGF-â production
by fibroblastic reticular LN stromal cells involved. Moreover, they
suggest that CTSL is able to negatively regulate the conversion
to Treg cells in non immunoprivileged sites.