Laminins affect T cell trafficking and allograft fate

Lymph nodes (LNs) are integral sites for the generation of immune tolerance and migration of CD4+ T cells, and induction of T-regs. Extracellular matrix proteins formed regions within the LN that were permissive for co-localization of alloantigen-presenting cells, alloreactive T cells, and T-regs. Laminin-411 is produced by vascular endothelial and promotes T cell migration. Laminin-511 and laminin-521 are also present in the endothelial basement membrane. However, laminin-511 and fails to promote T cell migration, although T cell co-stimulatory properties have been reported. Here they identified unique expression patterns of laminin proteins that correlated with alloantigen-specific immunity or immune tolerance in mice. Laminin α4 (R&D Systems Inc.) and LN-511 were used for in vitro experiments. The ratio of laminin α4 to laminin α5 was greater in domains within tolerant LNs, compared with immune LNs, and blocking laminin α4 function or inducing laminin α5 overexpression disrupted T cell and dendritic cells localization These data again were commensurate with the in vitro migration results whereby laminin α5 impeded while α4 permitted migration through the endothelium and associated basement membrane. Furthermore, reducing α4 laminin circumvented tolerance induction and induced cardiac allograft inflammation and rejection in murine models. This work identifies laminins as potential targets for immune modulation.