INVESTIGADORES
BEKINSCHTEIN Pedro Alejandro
artículos
Título:
Cathepsin-L influences the expression of extracellular matrix in lymphoid organs and plays a role in the regulation of thymic output and of peripheral T cell number.
Autor/es:
GABRIELA LOMBARDI; DALIA BURZYN; JULIANA MUNDINANO; PAULA BERGUER; PEDRO BEKINSCHTEIN; HECTOR COSTA; LILIAN FEDRA CASTILLO; ALEJANDRA GOLDMAN; ROBERTO MEISS; ISABEL PIAZZON; IRENE NEPOMNASCHY
Revista:
JOURNAL OF IMMUNOLOGY
Referencias:
Año: 2005 vol. 174 p. 7022 - 7032
ISSN:
0022-1767
Resumen:
Nackt mice, which are deficient in cathepsin-L (CTSL), show an early
impairment during positive selection in the context of class II MHC
molecules and as a consequence, the percentage and absolute number of
CD4(+) thymocytes are significantly decreased. In this study, we show
that lymph nodes from nackt mice are hypertrophied, showing normal
absolute numbers of CD4(+) T cells and marked increases in the number
of CD8(+) T lymphocytes. Basal proliferative levels are increased in
the CD4(+) but not in the CD8(+) population. Lymph node T cells show
increases in the expression of alpha(5), alpha(6), and beta(1) integrin
chains. These alterations correlate with increases in the expression of
extracellular matrix (ECM) components in lymph nodes. Interestingly,
laminin, fibronectin, and collagen I and IV are markedly decreased in
nackt thymus which shows an augmented output of CD8(+) cells. These
results demonstrate that a mutation in the Ctsl gene influences the
levels of ECM components in lymphoid organs, the thymic output, and the
number of T cells in the periphery. They further raise the possibility
that, by regulating the level of expression of ECM components in
lymphoid organs, CTSL is able to broadly affect the immune system.