Involvement of laminin and its receptor in abrogation of heart graft rejection by autoreactive T cells from Trypanosoma cruzi-infected mice
Silva-Barbosa, S.D.; Cotta-de-Almeida, V.; Riederer, I.; De Meis, J.; Dardenne, M.; Bonomo, A.; Savino, W.
Journal of Immunology 159(2): 997-1003
1997
ISSN/ISBN: 0022-1767 PMID: 9218622 Document Number: 481082
The involvement of laminin and its receptor, the very late antigen 6 (VLA-6) integrin, in CD4+ T cell-dependent autoreactivity was evaluated using a transplantation model for the autoimmune myocarditis occurring in mice chronically infected with Trypanosoma cruzi. Previous work had shown that syngeneic mouse hearts grafted in the ears of chronic chagasic recipients were rejected through a CD4+ T cell-dependent mechanism, and that rejection also occurred when cells from chagasic animals were transferred adjacent to hearts transplanted into naive recipients. In this study, a thick laminin network was observed to form during rejection, with donor-derived CD4+ T cells concentrated in the laminin-rich areas. Antibodies against both laminin and its receptor inhibited rejection of syngeneic hearts. The results suggest that interaction of the VLA-6 molecule with laminin is involved in triggering the antimyocardial autoreactive process by driving the influx of CD4+ T cells to the heart. They also support the concept that an antigen-specific T cell response, even an autoreactive one, can be modulated by in vivo interactions involving extracellular matrix ligands and receptors. As far as the authors know, this is the first in vivo evidence for laminin-mediated T cell echotaxis, with simultaneous experimental demonstration of ligand and receptor involvement. The findings also indicate that treatment with anti-VLA-6 antibodies can be effective in suppressing autoimmune disease activity.