Laminins affect T cell trafficking and allograft fate

Warren K.J., Iwami D., Harris D.G, Bromberg J.S., Burrell B.E.
The Journal of Clinical Investigation, 2014

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 was 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.

 

CCR2+CCR5+ T Cells Producing Matrix Metalloproteinase-9 and Osteopontin in the Pathogenesis of Multiple Sclerosis

Sato W., Tomita A., Ichikawa D., Lin Y., Kishida H., Miyake S., Ogawa M., Okamoto T., Murata M., Kuroiwa Y., Aranami T., Yamamura T.
Journal of Immunology, 2012

To recapitulate the glia limitans layered with parenchymal basal lamina experimentally, we coated the upper sides of Transwell membrane inserts. The upper sides of Transwell membrane inserts (8 mm; Corning) were coated with 10 mg/ml laminin-1 (Sigma) or 20 mg/ml laminin-121. After aspirating the laminin solutions, the membrane inserts were turned upside down, and normal human astrocytes (NHA) were seeded on the lower sides of the membrane inserts. T cells were stimulated, harvested, suspended in the fresh medium, and seeded onto the upper chambers. After 8 h, cell suspension was collected from the lower chambers after careful pipetting, and absolute numbers of migrated cells were calculated. The T-cell migration across the NHA layered with laminin-111 or -121 was less efficient compared with the migration across the untreated membrane or the membrane treated with laminin alone, thus, this model would exhibit barrier functions against the penetration of activated T cells.